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1 Supporting Information for Data Mining of Supersecondary Structure Homology between Light Chains of Immunogloblins and MHC Molecules: Absence of the Common Conformational Fragment in the Human IgM Rheumatoid Factor Hiroshi Izumi, *, Akihiro Wakisaka, Laurence A. Nafie,, and Rina K. Dukor Table of contents Core programming code S2 Supersecondary structure homology between light chains of immunoglobulins S3-S4 Supersecondary structure homology between MHC class I and light chain of immunoglobulin S5-S9 Comparison of supersecondary structure homology between Fab immunogloblin fragments (light chains and heavy chains), TCR, CD4, CD8, KIR, and LILR S10-S13 Supersecondary structure homology among MHC class I related molecules S14-S19 Quantification of supersecondary structure homology of light chain of immunoglobulin between subunits of proteins (516 subunits) and between fragments S20-S27 Interaction of CD4 with MHC class II S28 Interaction of CD8 with MHC class I S29 Interaction of KIR with MHC class I S30 Interaction of LILR with β-2 microglobulin S31 Comparison of conformational fragments of main chains among MHC class I related molecules S32 S1

2 Core programming code (python): datab2 = datab1.splitlines() datab3 = ''.join(datab2) datab4 = datab3.split('o') s1 = SequenceMatcher(None, dataa4, datab4) ratio1 = s1.ratio() ratioall = [ratio1] for i, elem in enumerate(dataa4): if len(elem) < 6: continue else: if elem in datab4: datab5 = datab4.index(elem) dataa6 = dataa4[i:] datab6 = datab4[datab5:] s2 = SequenceMatcher(None, dataa6, datab6) ratio2 = s2.ratio() ratioall.append(ratio2) else: continue ratiomax = max(ratioall) S2

3 Table S1. Supersecondary structure homology between light chains of immunogloblins (2imm, 2mcp: mouse). 8 Terms a and b mean α and β for conformational elements, respectively. Term X indicates indeterminable conformational element. Number 2immA 2mcpL Homology 2immA 2mcpL Homology Homology 2immA 2mcpL aa seq. (main chain) (main chain) strict fuzzy (side chain) (side chain) 1 ASP ASP X3a4a X4b4a 3b4aX 3b6aX 2 ILE ILE 3b3a4b 6a3a4b 3a1b 1b1b 3 VAL VAL 6a3a4b 6a3a4a 3b 3a 4 MET MET 6a3a4b 6a3b4a 3a3b3b 3a3a3a 5 THR THR 6a3b4b 6a3b4a 3aX 4bX 6 GLN GLN 6a3a4a 6a3a4a 3b1a6aX 3b1a6bX 7 SER SER 1a4b1b 6b4b1b 2aX 2aX 8 PRO PRO 3b4b4b 3b4b4a 2b 4a 9 SER SER 3b5a4b 6a1b4b 3aX 5bX 10 SER SER 1a4b4b 6b4b4b 2aX 1aX 11 LEU LEU 6b4b4b 6b3a4a 2b1a 6a3b 12 SER SER 6b3a4b 6b3b4a 1bX 1aX 13 VAL VAL 6b4b4b 6a4b4a 1a 2b 14 SER SER 6a4b4a 3b1b4a 3aX 2bX 15 ALA ALA 3a3a4b 2a3a4a 16 GLY GLY 2a1b4a 5b1b4b 17 GLU GLU 6a4b4b 3b4b4b 3b1b4aX 3b6b2bX 18 ARG ARG 3b3a4b 6b3a4b 1b1a3b6a4bXX 1b1a3a6a1bXX 19 VAL VAL 6b4b4b 6b4b4b 2a 1a 20 THR THR 6b3a4b 1a3b4b 3bX 3aX 21 MET MET 6b4b4b 6a4b4b 2b1a5b 2b6b5b 22 SER SER 6a3a4b 6b4b4a 3aX 2aX 23 CYS CYS 5b3a4b 2a3b4b 1bX 1bX 24 LYS LYS 6a3a4b 6a3a4b 1a1b1b2aX 4a1a1b2aX 25 SER SER 6a4b4b 6a4b4a 2bX 2bX 26 SER SER 3b1b4b 3b1b4a 2aX 2aX 27 GLN GLN 6b4b4a 6b3a4a 3b1a4aX 6a5a6aX 28 SER SER 3b3a4b 3a3a4b 1bX 1aX 29 LEU LEU 6a1a4b 6a1b4a 3b3a 3b3b 30 LEU LEU 3b3a4b 3b3a4a 1b1a 5a6b 31 ASN ASN 6a3b4b 3b3a4b 1a6aX 6b4bX 32 SER SER 3a5a4b 6a1a4a 4aX 2bX 33 GLY GLY 3a5b4a 6b5a4b 34 ASN ASN 6a1a4a 6a1b4a 2b6bX 3b4bX 35 GLN GLN 2b6b4a 2a6a4b 3b6a1bX 6a1a4bX 36 LYS LYS 6a3a4b 1a3a4b 1a1b4b6bX 3a5a3a1aX 37 ASN ASN 6a3a4b 6a4b4b 3b3bX 4b3bX 38 PHE PHE 3b6a4a 6a6a4a 3b3a 3a2b 39 LEU LEU 6b3a4b 6b3a4a 1a2b 1b6a 40 ALA ALA 6a4b4b 6a4b4b 41 TRP TRP 6b3a4b 6a3a4b 3b2aX 3b2aX 42 TYR TYR 6b4b4b 6a4b4b 3b2aX 3a2aX 43 GLN GLN 6a3a4b 6a3a4b 1b1a2bX 1b1a6aX 44 GLN GLN 6b3b4b 6b3b4a 1b1b2bX 1a1a4aX 45 LYS LYS 3b4b4b 3b4b4b 3b1a1a1bX 6a5a5a5bX 46 PRO PRO 3a3a4b 3a3b4b 4b 4b 47 GLY GLY 2a1a4b 2b6b4b 48 GLN GLN 6a4b4b 6b4b4b 3b1a4aX 3a1a2bX 49 PRO PRO 3b4b4b 3b4b4b 2b 4a 50 PRO PRO 3a3a4b 3b4b4b 4b 4b S3

4 51 LYS LYS 6b3a4b 6b3a4a 1b1a1b2bX 2a1b2b1aX 52 LEU LEU 3b3a4b 3a3a4a 1b1b 1a4a 53 LEU LEU 6a5a4b 6a5b4a 3b3b 6b4a 54 ILE ILE 6b3a4b 6b3a4b 3b1b 3a3b 55 TYR TYR 6b4b4b 6b4b4a 2b3bX 2b3bX 56 GLY GLY 2a1a4a 2a4a4a 57 ALA ALA 2a5a4a 6a1b4a 58 SER SER 6b1a4b 6b1b4b 2bX 2bX 59 THR THR 3b3b4a 3b3b4b 3aX 3aX 60 ARG ARG 3b3a4b 3b3a4b 3b1a3b3b4bXX 1b6b3a4b1aXX 61 GLU GLU 3b3a4a 3b3a4b 3b3b4bX 1b2b4aX 62 SER SER 3a3a4b 3a3a4b 1aX 1aX 63 GLY GLY 2a1a4b 5b5a4b 64 VAL VAL 3b3a4a 3b3a4b 3b 3b 65 PRO PRO 3b4b4a 3a3a4a 4a 4b 66 ASP ASP 3b1b4b 3b1a4b 2a4aX 2a4bX 67 ARG ARG 3b1b4a 3b5a4a 2a1b1a3b4bXX 3a1a3b5b4bXX 68 PHE PHE 6a3a4b 6a3a4a 3b3b 3a2a 69 THR THR 6b3b4a 6b3a4a 3bX 3bX 70 GLY GLY 6a4b4b 6b3a4a 71 SER SER 6b4b4b 6b4b4a 2bX 6aX 72 GLY GLY 5b4a4a 5b4b4b 73 SER SER 1a4b4b 1a4b4a 1bX 2aX 74 GLY GLY 2a2a4a 2a2a4a 75 THR THR 6a1b4a 6b1b4a 2bX 2aX 76 ASP ASP 6a3b4a 6b3b4b 3b4bX 3a6aX 77 PHE PHE 6b4b4a 6a4b4b 3b3b 3a2a 78 THR THR 6b3a4b 6b4b4a 3bX 2aX 79 LEU LEU 6b3a4b 1a3a4b 1a1a 1a4b 80 THR THR 6a3a4b 6b3a4b 3bX 3aX 81 ILE ILE 6a3a4b 6a3b4b 3a1b 3b5a 82 SER SER 3b1b4b 3b5a4b 2bX 5bX 83 SER SER 6b3b4a 6b6a4a 1bX 1bX 84 VAL VAL 3b3a4b 3a3a4a 3b 3a 85 GLN GLN 6a4b4a 6b4b4a 3b3a5aX 3b1a4aX 86 ALA ALA 3b5a4a 3a1b4b 87 GLU GLU 3b1a4b 6a1b4a 2a6b2aX 4a2a4bX 88 ASP ASP 3b1b4a 3b1b4a 3a3aX 3b4bX 89 LEU LEU 3b3a4a 3a3b4b 1b2a 1b2b 90 ALA ALA 1b4b4b 1a4a4b 91 VAL VAL 6a3a4a 6a3a4b 3b 3a 92 TYR TYR 6a3a4b 6a3b4b 3b2aX 3b6aX 93 TYR TYR 6b3a4b 6a3a4b 3b3bX 3b3bX 94 CYS CYS 5a4b4a 5a4b4b 2bX 2aX 95 GLN GLN 6b3a4b 6b4b4b 1a1a1aX 5a1a6bX 96 ASN ASN 3b3a4a 6a3b4b 5a2bX 5a6bX 97 ASP ASP 6a1a4a 6a1a4b 2a4aX 6b4bX 98 HIS HIS 6b1b4a 3b5b4b 1a2aX 1a3bX 99 SER SER 6a3a4b 1a4b4a 1bX 2bX 100 TYR TYR 3b3a1a 3b3a1b 3b2aX 3b5bX 101 PRO PRO 3b3a4a 3b3a4b 4a 4b 102 LEU LEU 3b4b4a 3b3a4a 3a3a 3b5a 103 THR THR 6b3a4b 6b4b4b 2bX 2bX 104 PHE PHE 6a3a4a 6b4b4b 3b2a 3a2a 105 GLY GLY 3b4b4a 6a4b4a 106 ALA ALA 3b1b4b 3b5a4a 107 GLY GLY 5b4b4b 5b4a4b 108 THR THR 6a3a4b 6b3b4b 3bX 3bX 109 LYS LYS 3b3a4a 3b3a4b 1a1b1b2aX 6a6a1a1bX 110 LEU LEU 6a3a4a 6a3a4b 1a3b 1b5b 111 GLU GLU 6b4b4b 6a3a4b 3a1b3bX 3a6b4aX 112 LEU ILE 6a3a4b 6a3a4b 3b6a 3b3b 113 LYS LYS 6a3a4b 6a4b4b 1a1a1b2aX 3a6a3b3bX 114 ARG ARG 3b6bX 1a4b4b 3b1b1b5b4bXX 2b5a3a5a4aXX % 11.5% 94.7% S4

5 Table S2. Supersecondary structure homology between MHC class I (1wbx: mouse) 13 and light chain of immunogloblin (2w9e: mouse). 14 Though homology of these amino acid sequences is low (11.7%), the characteristic fragment pattern ( aa., pale green: α- helix-type, orange: β-sheet-type) is common. Terms a and b mean α and β for conformational elements, respectively. Term X indicates indeterminable conformational element. Number 1wbxA 2w9eL Homology 1wbxA 2w9eL Homology Homology 1wbxA aa seq. (main chain) (main chain) strict fuzzy (side chain) 1 PRO X3a4a 4a 2 HIS 1a4b4a 3b3bX 3 SER 1a4b4b 2aX 4 MET 6b3a4b 1a1b2a 5 ARG 6b3a4b 3b3b1a3b4bXX 6 TYR 6a3a4b 3b2aX 7 PHE 6a3b4a 3b2b 8 GLU 6a3a4a 3a1b2aX 9 THR 6b3a4b 3bX 10 ALA 6a3a4a 11 VAL 6b3a4a 3b 12 SER 3b3a4a 2bX 13 ARG 6a3b4a 3a1a5a1a4bXX 14 PRO 3a3a4a 4b 15 GLY 5b1b4a 16 LEU 6a3a4a 3a3b 17 GLU 3b5a4a 1a2a1aX 18 GLU 6a3a4b 3a3b4bX 19 PRO 3b4b4b 4a 20 ARG 3b3a4a 1a1a1a1b4bXX 21 TYR 6b3a4b 1b2aX 22 ILE 6b3a4b 3a1b 23 SER 6b3a4b 1bX 24 VAL 6b3a4b 3a 25 GLY 6a3a4b 26 TYR 6b3a4b 3a2aX 27 VAL 6b3a4a 3b 28 ASP 2b6b4b 3b4aX 29 ASN 2a1a4b 3a3aX 30 LYS 6a3a4b 1b2a1b2bX 31 GLU 3a3a4a 1b1b4bX 32 PHE 6b1b4b 2a3b 33 VAL 6b4b4a 2b 34 ARG 1a3a4b 1b1b3b6a4bXX 35 PHE 6b3a4a 1b3b 36 ASP 6b3b4a 1a4bX 37 SER 3b1b4a 2aX 38 ASP 3b1b4b 6a1aX 39 ALA 3b4b4b 40 GLU 3b5a4b 1a1b4aX 41 ASN 6a6a4a 5a2bX 42 PRO 3a3a4b 4b 43 ARG 6b3a4b 6b1b1a2a4aXX 44 TYR 3b3a4b 6a3bX 45 GLU 6a3a4b 3a3b4bX 46 PRO 3b3a4b 4a 47 ARG 6b1a4b 3a3b3b1a4bXX 48 ALA 6b3a4b 49 PRO 3a5a4a 3a 50 TRP 3b1b4b 2b6aX 2w9eL (side chain) S5

6 51 MET 3b1b4b 3b3b3b 52 GLU 3a1b4b 2a1a3aX 53 GLN 3b1b4b 3a1a2bX 54 GLU 3b3a4b 3a3b1bX 55 GLY 3b4b4a 56 PRO 3a1b4a 4b 57 GLU 3b5a4b 3a2a2bX 58 TYR 3a5a4a 1b3bX 59 TRP 3b5a4a 3a5bX 60 GLU 3b5a4a 1b2a2bX 61 ARG 3b5a4a 1b1a2a6a4bXX 62 GLU 3b5a4b 3a3a4bX 63 THR 3a5a4b 3bX 64 GLN 3b5a4b 3b3a3aX 65 LYS 3b5a4b 3b1b2a1aX 66 ALA 3a5a4a 67 LYS 3b5a4b 4b6a6b1aX 68 GLY 3a5a4a 69 GLN 3b5a4b 3b3b5bX 70 GLU GLN 3a5a4b X6a4b 1a1b4bX 3a2a4bX 71 GLN ILE 3b5a4b 3b3a4b 3b3a5bX 3b1b 72 TRP VAL 3a5a4b 3b3b4b 1a5bX 3b 73 PHE LEU 3b5a4b 3b3a4b 3b2a 3b3a 74 ARG THR 3a5a4a 6a3b4b 1a1a5b6a4bXX 3aX 75 VAL GLN 3b5a4b 6a3a4b 3b 3b1b6aX 76 SER SER 3b5a4b 1a4b1b 3bX 2aX 77 LEU PRO 3a5a4b 3b4b4b 3b3b 4a 78 ARG ALA 3b5a4a 3b5a4b 1a1b3a5b4aXX 79 ASN ILE 3b5a4a 6b3a4a 3b4bX 1b1b 80 LEU MET 3b5a4b 1a3b4a 3b3b 1a1b5b 81 LEU SER 3a5a4a 6a3a4a 6b5a 5aX 82 GLY ALA 3b5a4a 6b3a4b 83 TYR SER 3a5a4a 3b3a4a 3b4bX 3aX 84 TYR PRO 6a1a4b 3b3a4a 3b3bX 4a 85 ASN GLY 2b6b4b 2a1b4b 1a4aX 86 GLN GLU 6a3a4b 3b3a4b 3b1b5aX 6a1a6bX 87 SER LYS 3b3a4b 3b3a4a 3bX 1a1b1a1bX 88 ALA VAL 3b4b4a 6b3a4b 3b 89 GLY THR 5b1b4b 6b3a4b 4bX 90 GLY MET 6a4b4b 6b3aX 2b1a2a 91 SER THR 6a3a4a XX4b 1aX XX 92 HIS CYS 6b4b4b 5b3b4a 3a3bX 1bX 93 THR SER 6b3a4b 6a3a4a 2aX 1bX 94 LEU ALA 6b3a4a 6a3a4a 1b1b 95 GLN SER 6b4b4b 3b5a4b 3a1b3bX 2aX 96 GLN SER 6b3a4b 6b4bX 1a1a4bX 4bX 97 MET SER 6b3a4b XX4b 3b1a3b XX 98 SER VAL 1a4b4b 6a4b4a 2aX 2a 99 GLY SER 1b4a4a 6a5a4b 3bX 100 CYS TYR 2a3a4b 6b3a4b 2bX 3a5bX 101 ASP MET 6a3a4b 6a3a4b 3b4bX 1a2a2a 102 LEU HIS 6a3a4b 6a3a4b 3a3a 3a3bX 103 GLY TRP 3b4a4b 6b3a4b 3a2aX 104 SER TYR 3b1b4b 6a4b4b 2bX 3b2aX 105 ASP GLN 3b1a4b 6a3a4b 2a4bX 1b1a5bX 106 TRP GLN 2a1b4b 6b3a4b 3b2aX 1a1a4aX 107 ARG LYS 3b4b4b 6a3a4b 3a1a1a1a4bXX 3b1b1a6aX 108 LEU SER 3a3a4b 3a3a4a 1a1a 2aX 109 LEU GLY 6a5a4b 5b5a4a 1b3b 110 ARG THR 1a3a4b 3b4b4b 1a1b1a1a4aXX 2aX 111 GLY SER 6a4b4a 3b4b4b 2aX 112 TYR PRO 6b3a4b 3a4b4b 3b2aX 4b 113 LEU LYS 1a3b4a 6b3a4b 1b1a 1b1a3b3bX 114 GLN ARG 6b3a4b 3a3a4a 3a1b2aX 1a1b2a1b4bXX 115 PHE TRP 6b3a4b 6a5a4b 3b2a 6b6aX 116 ALA ILE 6b3a4b 6b3a4b 3b1a 117 TYR TYR 6b3a4a 6b4b4a 1a2bX 2a3bX 118 GLU ASP 2b6b4b 2b6b4b 3a3b2bX 3b4aX 119 GLY THR 2a1a4b 2a5a4a 3bX 120 ARG SER 6b3a4b 6b1b4a 3a1a3b1b4aXX 2aX 121 ASP LYS 3a3a4b 3b3a4a 3b4bX 3a1a1a6aX 122 TYR LEU 6b5b4b 3b3a4b 1a2aX 3a3a S6

7 123 ILE ALA 6b4b4b 3b4b4a 1a1b 124 ALA SER 6b3a4b 3b3a4b 2aX 125 LEU GLY 3b3a4b 2a1a4b 1a1b 126 ASN VAL 3b4b4a 3b3a4b 3b1bX 3b 127 GLU PRO 3b1b4b 3b4b4a 1a1b4bX 4b 128 ASP ALA 3b1b4a 3b1b4a 2a4aX 129 LEU ARG 2b1a4a 3b1b4b 3a3a 2a1a1b6a4aXX 130 LYS PHE 6b5a4b 3b4b4b 3b1b1a2bX 3b6a 131 THR SER 6a4b4a 1a4b4b 2bX 2aX 132 TRP GLY 6a3a4b 6b3a4b 3a5bX 133 THR SER 6a3b4a 6b4a4b 3bX 2aX 134 ALA GLY 6a3a4a 5a4b4b 135 ALA SER 3b1b4b 1a4b4b 2aX 136 ASP GLY 6b4a4a 2a2a4a 2a4aX 137 MET THR 3b5a4a 6a1bX 1b1a3b 2bX 138 ALA SER 3a5a4b XX4b XX 139 ALA TYR 3b1b4b 6b3aX 3b6aX 140 GLN SER 3b1b4b XXX 3a3a4bX XX 141 ILE LEU 3a5a4b XX4a 3a1a XX 142 THR THR 3a5a4a 6b3a4b 3aX 3aX 143 ARG ILE 3a5a4b 6a3b4a 1b1b2a2a4aXX 3a1b 144 ARG SER 3b5a4b 3b1b4a 3b1b1a5a4aXX 2aX 145 LYS SER 3b5a4a 1a3b4a 1a1b2a5aX 1bX 146 TRP MET 3b5a4b 3b3a4a 3b4aX 1b2a1a 147 GLU GLU 3b5a4b 6b3a4a 3b1b4aX 6b2a2aX 148 GLN ALA 3a5a4a 3a5a4a 1b2a4aX 149 SER GLU 3b1b4a 3b1b4a 2aX 3a5b2aX 150 GLY ASP 2a6b4a 3b1b4b 3a4bX 151 ALA ALA 3b5a4a 3a3b4a 152 ALA ALA 3a1b4a 1a4b4b 153 GLU THR 3b5a4b 6a3a4a 6b2a2aX 3aX 154 HIS TYR 3a5a4b 6a3a4b 1b2aX 3b2aX 155 TYR PHE 3b5a4b 6a3a4b 3b3bX 3a3b 156 LYS CYS 3a5a4a 5a4b4a 1a1a5a2aX 2bX 157 ALA HIS 3b5a4b 6b3a4b 1a6bX 158 TYR GLN 3b5a4a 6b3a4a 1b2aX 2a2a6bX 159 LEU TRP 3b5a4b 6b6b4a 3b3b 3b4bX 160 GLU ARG 3b1b4a 3b5a4a 3b1b4bX 1b2a1b6a4bXX 161 GLY SER 6a5b4a 1a3a4b 2aX 162 GLU ASN 3a5a4a 3b3a1b 3b5b3bX 1a3aX 163 CYS PRO 1b5a4b 3b3a4b 1aX 4a 164 VAL TYR 3b5a4b 3b3a4a 3b 3a3bX 165 GLU THR 3a5a4a 6b4b4a 1b1a4bX 2bX 166 TRP PHE 3b5a4b 6a3a4b 3b5bX 3b5b 167 LEU GLY 3b5a4b 3b4b4b 1b1b 168 HIS GLY 3b5a4a 3b1b4a 3b2aX 169 ARG GLY 3b5a4a 2a3a4b 1b1b1b2a4aXX 170 TYR THR 3b5a4b 6a3a4b 3b3aX 3bX 171 LEU LYS 3b5a4b 3b3a4a 3b3b 1a1a6b1bX 172 LYS LEU 3b5a4a 6a3a4a 1a1b3a3aX 1b1a 173 ASN GLU 3b5a4a 6b3a4b 3b4aX 3b1b3aX 174 GLY ILE 6a1a4a 6a3a4b 1a1b 175 ASN LYS 3a5a4a 3b3a4b 1a3bX 3b1b1b3bX 176 ALA ARG 3b1b4b 6b4b4b 2b5a3b5a4aXX 177 THR ALA 6a5a4a 3b3a4b 2aX 178 LEU ASP 3b5a4a 3a3a4a 3b3b 3a4bX 179 LEU ALA 3b1b4a 6b3a4a 3b1a 180 ARG ALA 3b4b4b 3b4b4b 3b1a2a6a4bXX 181 THR PRO 6b4b4b 3b3a4b 2aX 4a 182 ASP THR 6b3b4b 3b3b4b 3b3bX 3aX 183 SER VAL 3b3a4b 3b3a4b 2aX 3a 184 PRO SER 3b3a4b 6b4b4b 4b 3aX 185 LYS ILE 6a3b4a 6b3a4a 3b1b1b5aX 1a1b 186 ALA PHE 6b4b4b 6b3a4b 3a2a 187 HIS PRO 1a4b4a 3b4b4b 2a3bX 4b 188 VAL PRO 6a3a4b 3b4b4b 3b 4b 189 THR SER 6a4b4a 6a4b4b 2bX 2bX 190 HIS SER 6b3a4a 3b5a4b 1a3bX 2aX 191 HIS GLU 6b3a4b 3a5a4a 3a5bX 6a2a4aX 192 PRO GLN 3b4b4b 3b5a4a 4b 1b5a2bX 193 ARG LEU 6b5b4b 3a5a4b 5a2b5a5b4bXX 3b3b 194 SER THR 1a4a4a 3b5a4b 2aX 3aX S7

8 195 LYS GLY 3a3b4b 3a5a4a 1a1b1b1aX 196 GLY GLY 2a1a4a 5a1b4a 197 GLU GLY 6b3a4a 6a4b4b 3b1a6aX 198 VAL ALA 6b4b4b 1a3b4a 2a 199 THR SER 6a3a4b 6a3b4b 3bX 3bX 200 LEU VAL 6a3a4b 6a3a4a 3a3a 3b 201 ARG VAL 6b3a4b 6a3a4b 1a5a2b6b4bXX 3a 202 CYS CYS 5a3b4a 5b3b4b 1aX 1aX 203 TRP PHE 6a3a4b 6a3b4b 3b2aX 3b3b 204 ALA LEU 6b3a4a 6a3b4a 3b1b 205 LEU ASN 6b4b4b 6a3a4b 3a3b 3b4bX 206 GLY ASN 2b6b4a 2b6b4a 3a2bX 207 PHE PHE 6a4b4b 6a4b4b 2b2a 2b3b 208 TYR TYR 1a3a1a 1a3a1a 1b2aX 1a3bX 209 PRO PRO 3b4a4a 3b4b4a 4a 4b 210 ALA LYS 3b1b4b 3b1b4a 2b1a1b1bX 211 ASP ASP 3b3a4a 3b3b4a 3a2aX 3a2aX 212 ILE ILE 1a4b4b 6b4b4b 1a1b 1a1b 213 THR ASN 6b3a4b 1a3a4b 3aX 1a4bX 214 LEU VAL 6a3a4b 6a4b4b 3a3b 4b 215 THR LYS 6b4b4b 6b3a4b 2aX 1a1b2a1aX 216 TRP TRP 6a3a4a 6a3a4b 3b5bX 3b5bX 217 GLN LYS 6b3a4b 6a3a4b 3b1b6bX 3b1a1b1aX 218 LEU ILE 6b3a4b 6a6a4a 1b1a 3a1b 219 ASN ASP 2b6b4b 2a6b4b 1a6aX 3b3aX 220 GLY GLY 2a1a4b 5b1b4b 221 GLU SER 6a3a4b 6a4b4a 3a3b4bX 3bX 222 GLU GLU 3b3a4b 3b3a4b 3a3b2bX 1a1a4aX 223 LEU ARG 3b6a4a 6b3a4b 3b3b 6b5b1b3a4aXX 224 THR GLN 3a5a4a 6b5a4a 3aX 3b1a2bX 225 GLN ASN 6a1a4a 3b3b4a 2b1b1bX 6b4aX 226 ASP GLY 6b1a4b 5b1a4b 3b3bX 227 MET VAL 6b4b4b 6a3a4b 2a1a5b 3b 228 GLU LEU 6a3b4a 6a3a4a 1a1b4aX 3b3a 229 LEU ASN 6a3b4b 6b3a4b 1a1a 3b5aX 230 VAL SER 3b4b4b 6b3a4a 6b 1aX 231 GLU TRP 3b3a4b 6b3a4b 3b2a4aX 3a6aX 232 THR THR 3a3a4a 6a4b4b 3bX 2bX 233 ARG ASP 6b3a4b 3b4a4a 2a1a1a1a4aXX 3b5aX 234 PRO GLN 3b3a4b 3b3a4b 4a 1a1b2bX 235 ASP 3b3a4a 1a2aX 236 ALA SER 3b1b4b 3b1b4b 2bX 237 GLY LYS 5b1b4a 6a5b4a 1a1b5a2bX 238 ASP ASP 6a1a4a 6a1a4b 2a4aX 2a4aX 239 GLY SER 5b1b4b 2a1a4a 3aX 240 THR THR 6a4b4a 6a4b4b 2aX 2bX 241 PHE TYR 6b4b4b 6a4b4b 3b5b 3a6aX 242 GLN SER 6b4b4b 6b4b4a 3a1a1bX 3bX 243 LYS MET 1a4b4b 6b4b4b 1a1b1a2aX 1a6b6b 244 TRP SER 6b4b4b 6b3a4b 2b6aX XX 245 ALA SER 6b3a4b 6b3a4a 1aX 246 SER THR 6b4b4b 6b3a4b 2aX 3aX 247 VAL LEU 6b3a4b 6a3b4a 2b 1b1a 248 VAL THR 6a3a4a 6a3a4b 3a 3aX 249 VAL LEU 6b4b4a 6b4a4b 2a 3a3a 250 PRO THR 3b3a4b 6a3a4b 4b 2bX 251 LEU LYS 3b3a4a 3a5a4b 1b1a 1a1a1b3bX 252 GLY ASP 5b1b4a 3b5a4a 3b2bX 253 LYS GLU 6a1a4a 3b5a4b 3b6a1a5aX 1a1a4aX 254 GLU TYR 3a5a4a 3b5a4a 3b5b5aX 1b2aX 255 GLN GLU 3b1b4b 3b1b4b 3b3a3aX 3b1a2bX 256 ASN ARG 3b1b4a 3b5a4a 3a1bX 6a1a6a1b4bXX 257 HIS 6a4b4a 3a6aX 258 ASN 6a5a4a 1b2aX 259 SER 6a3a4a 1aX 260 TYR TYR 6a3a4b 6b3a4a 3b2aX 3a6aX 261 THR THR 6b3a4b 6b3a4b 2bX 3bX S8

9 262 CYS CYS 5a3a4b 5a3a4a 1bX 1aX 263 ARG GLU 6a3a4a 6b3b4a 3b6b2a5a4aXX 1a1b4bX 264 VAL ALA 6b3a4a 6a3a4b 3a 265 TYR THR 6b3a4a 6a3a4b 3a2aX 3aX 266 HIS HIS 1a3a4a 6b4b4b 1a2aX 1a6aX 267 GLU LYS 3a5a4b 3b5a4a 3b1b3bX 1b6b3b3bX 268 GLY THR 3b1b4a 3a5a4a 2bX 269 LEU SER 6a3b4b 6a3a4b 3a3b 2aX 270 PRO THR 3a5a4b 3b1b4a 4b 1bX 271 GLU SER 6a3a4b 6b3a4b 1b2a4aX 3aX 272 PRO PRO 3b3a4b 3a3b4a 4b 3a 273 LEU ILE 3b3a4b 3b3a4a 3a3b 3a5a 274 THR VAL 6b3a4a 6b3a4b 3aX 3b 275 LEU LYS 6b4b4a 6b3a4a 3b6b 3b3b1a1aX 276 ARG SER 6b4b4b 6b4b4b 2b1a4a2a4aXX 3aX 277 TRP PHE 3b3a4b 6b4b4b 1b6bX 2a5b 278 GLU ASN 6a3b4a 6a4b4b 2b1a2aX 3a4aX 279 PRO ARG 3b1bX 3b6a4b 4a 1a5a2b5b4aXX 280 ASN 6b5a4b 3a5aX 281 GLU 6b6aX 6a2a1aX % 8.7% 54.9% S9

10 Table S3. Comparison of supersecondary structure homology between Fab immunogloblin fragments (light chains and heavy chains), TCR, CD4, CD8, KIR, and LILR. 8 Of particular interest, IgM rheumatoid factor (1adqL), heavy chains of Fab immunoglobulin fragments, TCR, CD4, CD8, KIR, and LILR do not have the characteristic fragment pattern (black frame: aa., pale green: α-helix-type, orange: β-sheet-type). LILR connect with the conformational fragments in β-2 microglobulins as a type of pair forms (blue frame: aa., string sohsss ). Num. ICSM18 2w9eL IgG 3hc0L IgM 2agjL IgM 1adqL ICSM18 2w9eH IgG 3hc0H IgM 2agjH IgM 1adqH TCR 2ckbA TCR 2ckbB CD4 1jl4D CD8 1akjD KIR 1efxD LILR 2dypD 1 VAL 2 HIS ILE 3 GLN ASP GLU ARG PRO PRO 4 ILE ILE ILE TYR GLU GLN PCA GLU GLN GLU SER LYS LYS LYS 5 VAL GLN VAL VAL VAL VAL VAL VAL SER ALA GLN PRO PRO PRO 6 LEU MET LEU LEU GLN GLN THR GLN VAL VAL PHE SER THR THR 7 THR THR THR THR LEU LEU LEU LEU THR THR ARG LEU LEU LEU 8 GLN GLN GLN GLN GLN VAL LYS VAL GLN GLN VAL LEU TRP TRP 9 SER SER SER GLN GLN GLU GLU PRO SER SER ALA ALA ALA 10 PRO PRO PRO PRO SER SER SER SER ASP PRO LYS PRO HIS GLU GLU 11 ALA SER GLY PRO GLY GLY GLY GLY ALA ARG LYS LEU PRO PRO PRO 12 ILE SER THR SER PRO ALA PRO GLY ARG ASN VAL ASP GLY ASP GLY 13 MET LEU LEU VAL GLU GLU THR GLY VAL LYS VAL ARG ARG SER SER 14 SER SER SER SER LEU VAL LEU LEU THR VAL LEU THR LEU VAL VAL 15 ALA ALA LEU VAL VAL LYS VAL VAL VAL ALA GLY TRP VAL ILE ILE 16 SER SER SER ALA LYS LYS LYS GLN SER VAL LYS ASN LYS THR THR 17 PRO VAL PRO PRO PRO PRO PRO PRO GLU THR LYS LEU SER GLN GLN 18 GLY GLY GLY GLY GLY GLY THR GLY GLY GLY GLY GLY GLU GLY GLY 19 GLU ASP GLU GLN SER SER GLN ARG ALA LYS ASP GLU GLU SER SER 20 LYS ARG ARG THR SER SER THR SER SER VAL THR THR THR PRO PRO 21 VAL VAL ALA ALA VAL VAL LEU LEU LEU THR VAL VAL VAL VAL VAL 22 THR THR THR ARG LYS LYS THR ARG GLN GLU GLU ILE THR THR 23 MET ILE LEU ILE ILE VAL LEU LEU LEU LEU LEU LEU LEU LEU LEU 24 THR THR SER THR SER SER THR SER ARG SER THR LYS GLN SER ARG 25 CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS 26 SER LYS ARG GLY LYS LYS THR VAL LYS ASN THR GLN TRP GLN GLN 27 ALA ALA ALA GLY ALA ALA PHE THR TYR GLN ALA VAL SER GLY GLY 28 SER SER SER ASN SER SER SER SER SER THR SER LEU ASP SER GLY 29 SER GLN GLU ASN ARG GLY GLY GLY TYR ASN GLN LEU VAL LEU GLN 30 SER ASN THR ILE ASN TYR PHE PHE SER HIS LYS SER ARG GLU GLU 31 VAL VAL VAL GLY THR THR SER THR ALA ASN LYS ASN PHE ALA THR 32 SER GLY SER SER PHE PHE LEU PHE THR MET SER PRO GLU GLN GLN 33 ILE ASN LYS THR THR THR ASP PRO TYR ILE THR 34 ASP ASP THR THR ASP TYR TRP GLN SER 35 TYR TYR THR TYR LEU TYR PHE GLY 36 ASN TYR GLY ALA PHE ARG HIS CYS 37 LEU LEU GLU MET TRP GLN TRP SER 38 ASP HIS GLY HIS TYR ASP LYS TRP 39 TRP TRP VAL TRP VAL THR ASN LEU 40 VAL VAL GLY VAL GLN GLY SER PHE 41 LYS ARG TRP ARG TYR HIS ASN GLN 42 GLN GLN ILE GLN PRO GLY GLN PRO 43 SER ALA ARG SER ARG LEU ILE ARG 44 TYR ASN LYS SER HIS PRO GLN PRO GLN ARG LYS GLY 45 MET VAL VAL VAL GLY GLY PRO GLY GLY LEU ILE ALA 46 HIS ALA ALA HIS LYS GLN PRO LYS LEU ILE LEU ALA 47 TRP TRP TRP TRP THR GLY GLY GLY GLN HIS GLY ALA 48 TYR TYR TYR TYR LEU LEU LYS LEU LEU TYR ASN SER 49 GLN GLN GLN GLN GLU GLU ALA GLU LEU SER GLN PRO LILR 3d2uD S10

11 50 GLN GLN GLN GLN TRP TRP LEU TRP LEU TYR GLY THR 51 LYS LYS LYS LYS ILE MET GLU VAL LYS GLY SER PHE 52 SER PRO PRO PRO GLY GLY PHE SER TYR ALA PHE LEU 53 GLY GLY GLY GLY LEU TYR GLY LEU LEU 54 THR LYS GLN GLN ASN TRP ALA GLY SER SER THR TYR 55 SER ALA ALA ALA VAL ILE PHE ILE GLY THR LYS LEU 56 PRO PRO PRO PRO TYR TYR ILE SER ASP GLU GLY SER 57 LYS LYS ARG VAL PRO PRO TYR TRP PRO LYS PRO GLN HIS GLU GLU 58 ARG SER LEU LEU ASN GLY TRP ASN VAL GLY SER ASN PHE TYR TYR 59 TRP LEU LEU VAL ASN ASN ASN THR VAL ASP LYS LYS LEU ARG ARG 60 ILE ILE ILE VAL GLY VAL ASP GLY GLN ILE LEU PRO LEU LEU LEU 61 TYR SER TYR TYR VAL HIS ALA THR GLY PRO ASN LYS HIS TYR TYR 62 ASP SER GLY ASP THR ALA LYS ILE VAL ASP ASP ALA ARG ARG ARG 63 THR ALA ALA ASP GLY GLN ARG ILE ASN GLY ARG ALA GLU GLU GLU 64 SER SER SER SER TYR TYR TYR TYR GLY TYR ALA GLU GLY LYS LYS 65 LYS TYR SER ASP ASN ASN ASN ALA PHE LYS ASP GLY LYS LYS LYS 66 LEU ARG ARG ARG GLN GLU PRO ASP GLU ALA SER LEU PHE SER THR 67 ALA TYR ALA PRO LYS LYS SER SER ALA SER ARG ASP LYS ALA ALA 68 SER SER THR PRO PHE PHE LEU VAL GLU ARG ARG THR ASP SER PRO 69 GLY GLY GLY GLY ARG LYS GLN LYS PHE PRO SER GLN THR TRP TRP 70 VAL VAL ILE ILE GLY GLY SER GLY SER SER LEU ARG LEU ILE ILE 71 PRO PRO PRO PRO LYS ARG ARG ARG LYS GLN TRP PHE HIS THR THR 72 ALA SER ASP GLU ALA VAL LEU PHE SER GLU ASP SER LEU ARG ARG 73 ARG ARG ARG ARG THR THR THR ILE ASN ASN GLN GLY ILE ILE ILE 74 PHE PHE PHE PHE LEU ILE ILE ILE SER GLY LYS GLY ARG PRO 75 SER SER SER SER THR THR THR SER SER ASN ARG GLU PRO GLN 76 GLY GLY GLY GLY VAL ALA LYS ARG LEU HIS GLU GLU 77 SER SER SER SER ASP ASP ASP ASP GLY HIS LEU LEU 78 GLY GLY GLY ASN LYS LYS ALA ASN ASP VAL VAL 79 SER SER SER SER SER SER SER ALA GLY LYS LYS 80 GLY GLY GLY GLY SER THR LYS LYS VAL ASN LYS 81 THR THR THR ASN SER SER LYS ASN ASP SER 82 SER ASP ASP THR THR THR GLN SER THR LYS 83 TYR PHE PHE ALA ALA ALA VAL LEU PHE PHE PHE PHE ALA GLY GLY 84 SER THR THR THR TYR TYR VAL TYR HIS SER PRO VAL ASN GLN GLN 85 LEU LEU LEU LEU MET MET LEU LEU LEU LEU LEU LEU PHE PHE PHE 86 THR THR SER THR GLU GLU THR GLN ARG ILE ILE THR SER ARG PRO 87 ILE ILE ILE ILE LEU LEU LEU MET LYS LEU ILE LEU ILE ILE ILE 88 SER SER SER SER HIS SER THR ASN ALA GLU LYS SER GLY PRO PRO 89 SER SER GLY ARG SER SER ASN SER SER LEU ASN ASP PRO SER SER 90 MET LEU LEU VAL LEU LEU LEU LEU VAL ALA LEU PHE MET ILE ILE 91 GLU GLN GLU GLU THR ARG ASP ARG HIS THR LYS ARG MET THR THR 92 ALA PRO PRO ALA SER SER PRO VAL TRP PRO ILE ARG GLN TRP TRP 93 GLU GLU GLU GLY GLU GLU VAL GLU SER SER GLU GLU ASP GLU GLU 94 ASP ASP ASP ASP ASP ASP ASP ASP ASP GLN ASP ASN LEU HIS HIS 95 ALA PHE PHE GLU SER THR THR THR SER THR SER GLU ALA THR ALA 96 ALA ALA VAL ALA ALA ALA ALA ALA ALA SER ASP GLY GLY GLY GLY 97 THR THR VAL ASP VAL VAL THR LEU VAL VAL THR TYR THR ARG ARG 98 TYR TYR TYR TYR TYR TYR TYR TYR TYR TYR TYR TYR TYR TYR TYR 99 PHE PHE TYR TYR TYR TYR TYR TYR PHE PHE ILE PHE ARG GLY ARG 100 CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS 101 HIS GLN GLN GLN ALA ALA ALA ALA ALA ALA GLU SER TYR GLN TYR 102 GLN GLN GLN VAL LEU ARG ARG LYS VAL SER VAL ALA GLY TYR TYR 103 TRP TYR TYR TRP TYR SER THR THR SER GLY GLU LEU SER TYR GLY 104 ASP TYR TRP SER ARG Xaa 105 SER TYR GLU GLY SER Xaa 106 ASP GLY TRP TYR Xaa 107 VAL PHE ASP VAL Xaa 108 ILE VAL Xaa 109 GLU ALA GLY VAL 110 PHE ALA PHE THR 111 ARG ASP ALA SER GLU ALA HIS SER 112 SER THR SER SER TYR SER THR ASP SER SER SER ASP 113 ASN TYR SER ASP TYR ALA LEU GLN ASN PRO ARG THR 114 PRO PRO PRO HIS PHE LEU TYR LYS SER TYR ALA ALA 115 TYR PHE ARG ALA SER PRO GLU HIS PHE GLU ILE GLN ARG GLY 116 THR THR THR VAL TYR TYR TYR TYR THR GLY GLU MET LEU TRP ARG 117 PHE PHE PHE PHE TRP TRP TRP TRP PHE ALA VAL TYR SER SER SER S11

12 118 GLY GLY GLY GLY GLY GLY GLY GLY GLY GLY GLN PHE ALA GLU GLU 119 GLY GLN GLN GLY GLN GLN GLN GLN SER THR LEU SER PRO LEU SER 120 GLY GLY GLY GLY GLY GLY GLY GLY GLY ARG LEU HIS SER SER SER 121 THR THR THR THR THR THR THR ILE THR LEU VAL PHE ASP ASP ASP 122 LYS LYS LYS LYS LEU THR LEU LEU LYS SER PHE VAL PRO PRO PRO 123 LEU VAL VAL LEU VAL VAL VAL VAL VAL VAL GLY PRO LEU LEU LEU 124 GLU GLU GLU THR THR THR THR THR ILE LEU LEU VAL ASP VAL GLU 125 ILE ILE ILE VAL VAL VAL VAL VAL VAL GLU THR PHE ILE LEU LEU 126 LYS LYS LYS LEU SER SER SER SER LEU ASP ALA LEU VAL VAL VAL 127 ARG ARG ARG GLY SER SER SER SER PRO LEU ASN PRO ILE MET VAL 128 ALA THR THR GLN ALA ALA GLY GLY TYR ARG SER ALA THR THR THR 129 PRO LYS SER SER SER ASN ASP GLY GLY GLY 130 ASP VAL VAL LYS THR THR ALA ALA VAL THR LEU ALA ALA 131 ALA ALA ALA ALA THR LYS SER SER ILE THR HIS TYR TYR TYR 132 ALA ALA ALA ALA PRO GLY ALA ALA GLN PRO LEU GLU PRO ILE 133 PRO PRO PRO PRO PRO PRO PRO PRO ASN LYS LEU LYS LYS LYS 134 THR SER SER SER SER SER THR THR PRO VAL GLN PRO PRO PRO 135 VAL VAL VAL VAL VAL VAL LEU LEU GLU SER GLY SER THR THR 136 SER PHE PHE THR TYR PHE PHE PHE PRO LEU GLN LEU LEU LEU 137 ILE ILE ILE LEU PRO PRO PRO PRO ALA PHE SER SER SER SER 138 PHE PHE PHE PHE LEU LEU LEU LEU VAL GLU LEU ALA ALA ALA 139 PRO PRO PRO PRO ALA ALA VAL VAL TYR PRO THR GLN GLN GLN 140 PRO PRO PRO PRO PRO PRO SER SER ALA SER LEU PRO PRO PRO 141 SER SER SER SER GLY SER CYS CYS LEU LYS THR GLY SER SER 142 SER ASP ASP SER SER SER GLU GLU LYS ALA LEU PRO PRO PRO 143 GLU GLU GLU GLU ALA Xaa ASN ASN Xaa GLU GLU THR VAL VAL 144 GLN GLN GLN GLU ALA Xaa SER SER Xaa ILE SER VAL VAL VAL 145 LEU LEU LEU LEU GLN Xaa SER ASN ASP ALA PRO LEU THR ASN 146 THR LYS LYS GLN THR Xaa PRO PRO PRO ASN PRO ALA SER SER 147 GLY SER SER ALA ASN GLY SER SER ARG LYS GLY GLY GLY GLY 148 GLY GLY GLY ASN GLY SER SER SER GLN SER GLU GLY GLY 149 GLY THR THR LYS SER THR THR THR GLN LYS SER SER ARG ASN 150 ALA ALA ALA ALA VAL ALA VAL VAL ASP ALA PRO VAL VAL VAL 151 SER SER SER THR THR ALA ALA ALA SER THR SER THR THR THR 152 VAL VAL VAL LEU LEU LEU VAL VAL THR LEU VAL LEU LEU LEU 153 VAL VAL VAL VAL GLY GLY GLY GLY LEU VAL GLN SER GLN GLN 154 CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS 155 PHE LEU LEU LEU LEU LEU LEU LEU LEU LEU ARG SER GLU ASP 156 LEU LEU LEU ILE VAL VAL ALA ALA PHE ALA SER SER SER SER 157 ASN ASN ASN SER LYS LYS GLN GLN THR ARG PRO ARG GLN GLN 158 ASN ASN ASN ASP GLY ASP ASP ASP ASP GLY ARG SER VAL VAL 159 PHE PHE PHE PHE TYR TYR PHE PHE PHE PHE GLY SER ALA ALA 160 TYR TYR TYR TYR PHE PHE LEU LEU LYS TYR PHE PHE 161 PRO PRO PRO PRO PRO PRO PRO PRO ASP PRO ASN ASP GLY ASP 162 LYS ARG ARG GLY GLU GLU ASP ASP SER ASP ILE MET GLY GLY 163 ASP GLU GLU ALA PRO PRO SER SER GLN HIS GLN TYR PHE PHE 164 ILE ALA ALA VAL VAL VAL ILE ILE ILE VAL GLY HIS ILE ILE 165 ASN LYS LYS THR THR THR THR THR ASN GLU GLY LEU LEU LEU 166 VAL VAL VAL VAL VAL VAL PHE PHE VAL LEU LYS SER CYS CYS 167 LYS GLN GLN ALA THR SER SER SER PRO SER THR ARG LYS LYS 168 TRP TRP TRP TRP TRP TRP TRP TRP LYS TRP LEU GLU GLU GLU 169 LYS LYS LYS LYS ASN ASN LYS LYS THR VAL SER Xaa Xaa 170 ILE VAL VAL ALA SER SER TYR TYR MET ASN VAL GLY Xaa Xaa 171 ASP ASP ASP ASP GLY GLY LYS LYS GLU GLY SER GLU Xaa Xaa 172 GLY ASN ASN GLY SER ALA ASN ASN SER LYS GLN ALA GLU Xaa 173 SER ALA ALA SER LEU LEU ASN ASN GLY GLU LEU HIS HIS Xaa 174 GLU LEU LEU PRO SER THR SER SER VAL GLU GLU PRO Xaa 175 ARG GLN GLN VAL SER SER ASP ASP HIS LEU CYS GLN GLN 176 GLN SER SER LYS GLY GLY ILE ILE SER GLN ARG CYS CYS 177 ASN GLY GLY ALA VAL VAL SER SER GLY ASP PHE LEU LEU 178 GLY ASN ASN GLY HIS HIS SER SER VAL SER SER ASN ASN 179 VAL SER SER VAL THR THR SER GLY ALA SER SER 180 LEU GLN GLN GLU ARG ARG THR THR GLY GLN Xaa 181 ASN GLU GLU THR GLY GLY ASP TRP PRO Xaa Xaa 182 SER SER SER THR THR THR PHE PHE THR PRO THR LYS Xaa Xaa 183 TRP VAL VAL THR PHE PHE PRO PRO PHE GLN CYS VAL Xaa Xaa 184 THR THR THR PRO PRO PRO SER SER ILE ALA THR ASN Xaa Xaa 185 ASP GLU GLU SER ALA ALA VAL VAL THR TYR VAL GLY Xaa Xaa S12

13 186 GLN GLN GLN LYS VAL VAL LEU LEU ASP LYS LEU THR SER Xaa 187 ASP ASP ASP GLN LEU LEU ARG ARG ALA GLU GLN PHE SER SER 188 SER SER SER SER GLN GLN GLY GLY THR SER ASN GLN ARG ARG 189 LYS LYS LYS SER SER GLY GLY VAL ASN GLN ALA ALA ALA 190 ASP ASP ASP ASN SER LYS LYS LEU TYR LYS ASP ILE ILE 191 SER SER SER ASN ASP GLY TYR TYR ASP SER LYS PHE PHE PHE 192 THR THR THR LYS LEU LEU ALA ALA MET TYR VAL PRO SER SER 193 TYR TYR TYR TYR TYR TYR ALA ALA LYS CYS GLU LEU VAL VAL 194 SER SER SER ALA THR SER THR THR ALA LEU PHE GLY GLY GLY 195 MET LEU LEU ALA LEU LEU SER SER MET SER LYS PRO PRO PRO 196 SER SER SER SER SER SER GLN GLN ASP ARG ILE ALA VAL VAL 197 SER SER SER SER SER SER VAL VAL SER LEU ASP THR SER SER 198 THR THR THR TYR SER VAL LEU LEU LYS ARG ILE HIS PRO PRO 199 LEU LEU LEU LEU VAL VAL LEU LEU SER VAL VAL GLY ASN SER 200 THR THR THR SER THR THR PRO PRO ASN SER VAL GLY ARG ARG 201 LEU LEU LEU LEU VAL VAL SER SER GLY ALA LEU ARG ARG 202 THR SER SER THR PRO PRO LYS LYS ALA THR ALA TRP TRP 203 LYS LYS LYS PRO SER SER ASP ASP ILE PHE 204 ASP ALA ALA GLU SER SER VAL VAL ALA TRP 205 GLU ASP ASP GLN THR SER MET MET TRP HIS 206 TYR TYR TYR TRP TRP LEU GLN GLN SER 207 GLU GLU GLU LYS PRO GLY GLY GLY ASN 208 ARG LYS LYS SER SER THR THR THR ASN PRO 209 HIS HIS HIS HIS GLN GLN ASP ASN GLN ARG 210 ASN LYS LYS LYS GLU GLU THR ASN 211 SER VAL VAL SER SER THR HIS HIS SER HIS THR SER TRP 212 TYR TYR TYR TYR VAL TYR VAL VAL PHE PHE TYR HIS TYR 213 THR ALA ALA SER THR ILE VAL VAL THR ARG ARG ARG ARG 214 CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS 215 GLU GLU GLU GLN ASN ASN LYS LYS GLN GLN PHE TYR TYR 216 ALA VAL VAL VAL VAL VAL VAL VAL ASP VAL GLY GLY ALA 217 THR THR THR THR ALA ASN GLN GLN ILE GLN SER TYR TYR 218 HIS HIS HIS HIS HIS HIS HIS HIS PHE PHE PHE ASP ASP 219 LYS GLN GLN GLU PRO LYS PRO PRO LYS HIS ARG LEU SER 220 THR GLY GLY GLY ALA PRO ASN ASN GLU GLY ASP ASN ASN 221 SER LEU LEU SER SER SER GLY GLY THR LEU SER SER SER 222 THR SER SER THR SER ASN ASN ASN Xaa SER PRO PRO PRO 223 SER SER SER VAL THR THR LYS LYS Xaa GLU TYR TYR TYR 224 PRO PRO PRO GLU ALA LYS GLU GLU Xaa ASP GLU VAL GLU 225 ILE VAL VAL LYS VAL VAL LYS LYS Xaa LYS TRP TRP TRP 226 VAL THR THR THR ASP ASP ASP ASP ASN TRP SER SER SER 227 LYS LYS LYS VAL LYS LYS VAL VAL ALA PRO ASN SER LEU 228 SER SER SER ALA LYS LYS PRO PRO THR GLU SER PRO PRO 229 PHE PHE PHE PRO ILE VAL LEU LEU TYR GLY SER SER SER 230 ASN ASN ASN THR ALA GLU PRO PRO SER ASP ASP ASP 231 ARG ARG ARG GLU PRO PRO VAL SER PRO PRO LEU LEU 232 ASN GLY GLY CYS ALA LYS VAL SER LYS LEU LEU LEU 233 GLU GLU SER ILE ASP PRO LEU GLU GLU 234 CYS VAL VAL VAL LEU LEU 235 PRO THR SER LEU LEU 236 CYS GLN VAL VAL VAL 237 ASN ILE LEU 238 ILE GLY 239 SER 240 ALA 241 GLU 242 ALA 243 TRP 244 GLY 245 ARG 246 ALA 247 ASP 248 CYS 249 S13

14 Table S4. Supersecondary structure homology among MHC class I related molecules. 8 Though homology of these amino acid sequences is low, the characteristic fragment pattern ( aa., pale green: α-helix-type, orange: β-sheet-type) is common. As notable exceptions, UL18, CD1D, CD1A1, MIC-A, and MIC-B do not have the fragment patterns. Num. HLA-A2 1akjA HLA-A2 2vlrA HLA-B 2bsrA HLA-B 2cikA H2-DB 1wbxA H2-KB 1p4lA HLA-E 3bzeA HLA-G 2dypA UL18 3d2uA CD1D 1cd1A 1 GLU 2 ASN 3 GLN ALA 4 MET MET ASP ASP GLU 5 GLY GLY GLY GLY GLU GLU ARG ARG GLY GLY PRO 6 SER SER SER SER PRO PRO SER SER PRO PRO SER SER ARG ARG ARG 7 HIS HIS HIS HIS HIS HIS HIS HIS ASN SER HIS HIS HIS HIS TYR TYR LEU LEU 8 SER SER SER SER SER SER SER SER HIS TYR TYR HIS SER SER SER SER SER SER PRO SER 9 MET MET MET MET MET LEU LEU MET VAL THR THR MET LEU LEU LEU LEU LEU LEU LEU LEU 10 ARG ARG ARG ARG ARG ARG LYS ARG LEU PHE PHE LEU ARG ARG HIS HIS THR THR MET LEU 11 TYR TYR TYR TYR TYR TYR TYR TYR ARG ARG ARG LYS TYR TYR TYR TYR TYR TYR TYR TYR 12 PHE PHE PHE PHE PHE PHE PHE PHE TYR CYS CYS LEU ASN ASN LEU LEU ILE ILE HIS HIS 13 PHE PHE HIS TYR GLU VAL HIS SER GLY LEU LEU LEU LEU LEU PHE PHE TYR TYR LEU LEU 14 THR THR THR THR THR THR THR ALA TYR GLN GLN HIS THR MET MET MET THR THR ALA THR 15 SER SER SER ALA ALA ALA SER ALA THR MET MET PHE VAL VAL GLY GLY GLY GLY ALA ALA 16 VAL VAL VAL MET VAL VAL VAL VAL GLY SER SER ALA LEU LEU ALA ALA LEU LEU VAL VAL 17 SER SER SER SER SER SER SER SER ILE SER SER THR SER SER SER SER SER SER SER SER 18 ARG ARG ARG ARG ARG ARG ARG ARG PHE PHE PHE PHE TRP GLN GLU GLU LYS LYS ASP SER 19 PRO PRO PRO PRO PRO PRO PRO PRO ASP ALA ALA GLN ASP ASP GLN GLN HIS HIS LEU PRO 20 GLY GLY GLY GLY GLY GLY GLY GLY ASP ASN ASN ASN GLY GLY ASP ASP VAL VAL SER ALA 21 ARG ARG ARG ARG LEU LEU ARG ARG THR ARG ARG SER SER SER LEU LEU GLU GLU THR PRO 22 GLY GLY GLY GLY GLU GLY GLY GLY SER SER SER THR VAL VAL GLY GLY ASP ASP GLY GLY 23 GLU GLU GLU GLU GLU GLU GLU GLU HIS TRP TRP SER GLN GLN LEU LEU VAL VAL LEU THR 24 PRO PRO PRO PRO PRO PRO PRO PRO MET SER SER VAL SER SER SER SER PRO PRO PRO PRO 25 ARG ARG ARG ARG ARG ARG ARG ARG THR ARG ARG LEU GLY GLY LEU LEU ALA ALA SER ALA 26 PHE PHE PHE PHE TYR TYR PHE PHE LEU THR THR VAL PHE PHE PHE PHE PHE PHE PHE PHE 27 ILE ILE ILE ILE ILE MET ILE ILE THR ASP ASP GLY LEU LEU GLU GLU GLN GLN TRP TRP 28 ALA ALA THR ALA SER GLU SER ALA VAL SER SER GLY THR ALA ALA ALA ALA ALA ALA VAL 29 VAL VAL VAL VAL VAL VAL VAL MET VAL VAL VAL LEU GLU GLU LEU LEU LEU LEU THR SER 30 GLY GLY GLY GLY GLY GLY GLY GLY GLY VAL VAL GLY VAL GLY GLY GLY GLY GLY GLY GLY 31 TYR TYR TYR TYR TYR TYR TYR TYR ILE TRP TRP LEU HIS HIS TYR TYR SER SER TRP TRP 32 VAL VAL VAL VAL VAL VAL VAL VAL PHE LEU LEU LEU LEU LEU VAL VAL LEU LEU LEU LEU 33 ASP ASP ASP ASP ASP ASP ASP ASP ASP GLY GLY GLY ASP ASP ASP ASP ASN ASN GLY GLY 34 ASP ASP ASP ASP ASN ASP ASP ASP GLY ASP ASP ASP GLY GLY ASP ASP ASP ASP ALA PRO 35 THR THR THR THR LYS THR THR THR GLN LEU LEU VAL GLN GLN GLN GLN LEU LEU GLN GLN 36 GLN GLN LEU GLN GLU GLU GLN GLN HIS GLN GLN LYS PRO PRO LEU LEU GLN GLN GLN GLN 37 PHE PHE PHE PHE PHE PHE PHE PHE PHE THR THR MET PHE PHE PHE PHE PHE PHE TYR TYR 38 VAL VAL VAL VAL VAL VAL VAL VAL PHE HIS HIS GLY LEU LEU VAL VAL PHE PHE LEU LEU 39 ARG ARG ARG ARG ARG ARG ARG ARG THR ARG ARG SER ARG ARG PHE PHE ARG ARG THR SER 40 PHE PHE PHE PHE PHE PHE PHE PHE TYR TRP TRP LEU CYS TYR TYR TYR TYR TYR TYR TYR 41 ASP ASP ASP ASP ASP ASP ASP ASP HIS SER SER ASP ASP ASP ASP ASP ASN ASN ASN ASN 42 SER SER SER SER SER SER ASN SER VAL ASN ASN SER ARG ARG HIS HIS SER SER ASN SER 43 ASP ASP ASP ASP ASP ASP ASP ASP GLN ASP ASP ARG GLN GLN GLU GLU LYS LYS LEU LEU 44 ALA ALA ALA ALA ALA ALA ALA SER SER SER SER THR LYS LYS SER SER ASP ASP ARG ARG 45 ALA ALA ALA ALA GLU GLU ALA ALA SER ALA ALA GLY CYS ARG ARG ARG ARG ARG GLN GLY 46 SER SER SER SER ASN ASN SER SER ASP THR THR ASN ARG ARG ARG ARG LYS LYS GLU GLU CD1D 2fikA CD1A1 3jvgA MIC-A 1hyrC MIC-B 1je6A HFE 1a6zA HFE 1de4A ZAG 1zagA ZAG 3es6A FCRN 1frtA FCRN 3m17A S14

15 47 GLN GLN PRO PRO PRO PRO PRO PRO LYS ILE ILE ILE ALA ALA VAL VAL SER SER ALA ALA 48 ARG ARG ARG ARG ARG ARG ARG ARG ALA SER SER ARG LYS LYS GLU GLU GLN GLN ASP GLU 49 MET MET GLU THR TYR TYR MET MET SER PHE PHE TYR PRO PRO PRO PRO PRO PRO PRO PRO 50 GLU GLU GLU GLU GLU GLU VAL GLU SER THR THR TYR GLN GLN ARG ARG MET MET CYS CYS 51 PRO PRO PRO PRO PRO PRO PRO PRO ARG LYS LYS ARG GLY GLY THR THR GLY GLY GLY GLY 52 ARG ARG ARG ARG ARG ARG ARG ARG ALA PRO PRO PRO GLN GLN PRO PRO LEU LEU ALA ALA 53 ALA ALA ALA ALA ALA ALA ALA ALA ASN TRP TRP TRP TRP TRP TRP TRP TRP TRP TRP TRP 54 PRO PRO PRO PRO PRO ARG PRO PRO GLY SER SER LEU ALA ALA VAL VAL ARG ARG ILE VAL 55 TRP TRP TRP TRP TRP TRP TRP TRP THR GLN GLN ARG GLU GLU SER SER GLN GLN TRP TRP 56 ILE ILE ILE ILE MET MET MET VAL ILE GLY GLY PRO ASP ASP SER SER VAL VAL GLU GLU 57 GLU GLU GLU GLU GLU GLU GLU GLU SER LYS LYS SER VAL VAL ARG ARG GLU GLU ASN ASN 58 GLN GLN GLN GLN GLN GLN GLN GLN TRP LEU LEU LEU LEU LEU ILE ILE GLY GLY GLN GLN 59 GLU GLU GLU GLU GLU GLU GLU GLU MET SER SER PRO GLY GLY SER SER MET MET VAL VAL 60 GLY GLY GLY GLY GLY GLY GLY GLY ALA ASN ASN LYS ASN ALA SER SER GLU GLU SER SER 61 PRO PRO PRO PRO PRO PRO SER PRO ASN GLN GLN GLY LYS GLU GLN GLN ASP ASP TRP TRP 62 GLU GLU GLU GLU GLU GLU GLU GLU VAL GLN GLN ASP THR THR MET MET TRP TRP TYR TYR 63 TYR TYR TYR TYR TYR TYR TYR TYR SER TRP TRP TRP TRP TRP TRP TRP LYS LYS TRP TRP 64 TRP TRP TRP TRP TRP TRP TRP TRP ALA GLU GLU ASP ASP ASP LEU LEU GLN GLN GLU GLU 65 ASP ASP ASP ASP GLU GLU ASP GLU ALA LYS LYS VAL ARG THR GLN GLN ASP ASP LYS LYS 66 GLY GLY ARG ARG ARG ARG ARG GLU TYR LEU LEU ILE GLU GLU LEU LEU SER SER GLU GLU 67 GLU GLU GLU ASN GLU GLU GLU GLU PRO GLN GLN GLU THR THR SER SER GLN GLN THR THR 68 THR THR THR THR THR THR THR THR THR HIS HIS SER ARG GLU GLN GLN LEU LEU THR THR 69 ARG ARG GLN GLN GLN GLN ARG ARG TYR MET MET SER ASP ASP SER SER GLN GLN ASP ASP 70 LYS LYS ILE ILE LYS LYS SER ASN LEU PHE PHE ILE LEU LEU LEU LEU LYS LYS LEU LEU 71 VAL VAL CYS PHE ALA ALA ALA THR ASP GLN GLN LYS THR THR LYS LYS ALA ALA LYS ARG 72 LYS LYS LYS LYS LYS LYS ARG LYS GLY VAL VAL SER GLY GLU GLY GLY ARG ARG SER ILE 73 ALA ALA ALA THR GLY GLY ASP ALA GLU TYR TYR TYR ASN ASN TRP TRP GLU GLU LYS LYS 74 HIS HIS LYS ASN GLN ASN THR HIS ARG ARG ARG VAL GLY GLY ASP ASP ASP ASP GLU GLU 75 SER SER ALA THR GLU GLU ALA ALA ALA VAL VAL ARG LYS GLN HIS HIS ILE ILE GLN LYS 76 GLN GLN GLN GLN GLN GLN GLN GLN LYS SER SER ASP ASP ASP MET MET PHE PHE LEU LEU 77 THR THR THR THR TRP SER ILE THR GLY PHE PHE PHE LEU LEU PHE PHE MET MET PHE PHE 78 HIS HIS ASP TYR PHE PHE PHE ASP ASP THR THR SER ARG ARG THR THR GLU GLU LEU LEU 79 ARG ARG ARG ARG ARG ARG ARG ARG LEU ARG ARG ARG MET ARG VAL VAL THR THR GLU GLU 80 VAL VAL GLU GLU VAL VAL VAL MET ILE ASP ASP LEU THR THR ASP ASP LEU LEU ALA ALA 81 ASP ASP ASP SER SER ASP ASN ASN PHE ILE ILE VAL LEU LEU PHE PHE LYS LYS ILE PHE 82 LEU LEU LEU LEU LEU LEU LEU LEU ASN GLN GLN GLN ALA THR TRP TRP ASP ASP ARG LYS 83 GLY GLY ARG ARG ARG ARG ARG GLN GLN GLU GLU MET HIS HIS THR THR ILE ILE THR ALA 84 THR THR THR ASN ASN THR THR THR THR LEU LEU TYR ILE ILE VAL VAL LEU 85 LEU LEU LEU LEU LEU LEU LEU LEU GLU VAL VAL THR MET MET GLU GLU GLU 86 ARG ARG LEU ARG LEU LEU ARG ARG GLN LYS LYS GLU GLU TYR TYR ASN 87 GLY GLY ARG GLY GLY GLY GLY GLY ASN MET Xaa ASN ASN TYR TYR GLN 88 TYR TYR TYR TYR TYR TYR TYR TYR LEU MET Xaa HIS HIS 89 TYR TYR TYR TYR TYR TYR TYR TYR LEU SER Xaa 90 GLU PRO Xaa 91 LEU 92 GLU 93 ILE ILE ILE 94 ASN ASN ASN ASN ASN ASN ASN ASN ALA LYS LYS 95 GLN GLN GLN GLN GLN GLN GLN GLN LEU ASP ASP ASN ASN ASN ASN LEU 96 SER SER SER SER SER SER SER SER GLY LYS Xaa Xaa GLN GLN HIS HIS ASP ASP GLY S15

16 97 GLU GLU GLU GLU ALA LYS GLU GLU TYR GLU Xaa VAL LYS LYS SER SER SER SER ILE GLY 98 ALA ALA ALA ALA GLY GLY ALA ALA ARG ASP Xaa PRO GLU GLY LYS LYS ASN ASN ASN LYS 99 GLY GLY GLY GLY GLY GLY GLY SER SER TYR TYR TYR GLY GLY GLU GLU GLY GLY GLY GLY 100 SER SER SER SER SER SER SER SER GLN PRO PRO PRO LEU LEU SER SER SER SER THR PRO 101 HIS HIS HIS HIS HIS HIS HIS HIS SER ILE ILE PHE HIS HIS HIS HIS HIS HIS PHE TYR 102 THR THR THR ILE THR THR THR THR VAL GLU GLU VAL SER SER THR THR VAL VAL THR THR 103 VAL VAL LEU ILE LEU ILE LEU LEU LEU ILE ILE PHE LEU LEU LEU LEU LEU LEU LEU LEU 104 GLN GLN GLN GLN GLN GLN GLN GLN THR GLN GLN GLN GLN GLN GLN GLN GLN GLN GLN GLN 105 ARG ARG ASN ARG GLN VAL TRP TRP TRP LEU LEU SER GLU GLU VAL VAL GLY GLY GLY GLY 106 MET MET MET MET MET ILE MET MET THR SER SER SER ILE ILE ILE ILE ARG ARG LEU LEU 107 TYR TYR TYR TYR SER SER HIS ILE HIS ALA ALA ILE ARG ARG LEU LEU PHE PHE LEU LEU 108 GLY GLY GLY GLY GLY GLY GLY GLY GLU GLY GLY GLY VAL VAL GLY GLY GLY GLY GLY GLY 109 CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS 110 ASP ASP ASP ASP ASP GLU GLU ASP ASN GLU GLU GLU GLU GLU GLU GLU GLU GLU GLU GLU 111 VAL VAL VAL LEU LEU VAL LEU LEU THR MET MET LEU ILE ILE MET MET ILE ILE LEU LEU 112 GLY GLY GLY GLY GLY GLY GLY GLY THR TYR TYR GLN HIS HIS GLN GLN GLU GLU ALA GLY 113 SER SER PRO PRO SER SER PRO SER GLU PRO PRO SER GLU GLU GLU GLU ASN ASN PRO PRO 114 ASP ASP ASP ASP ASP ASP ASP ASP ASN GLY GLY ASN ASP ASP ASP ASP ASN ASN ASP ASP 115 TRP TRP GLY GLY TRP GLY ARG GLY GLY ASN ASN GLY ASN SER ASN ASN ARG ARG ASN ASN 116 ARG ARG ARG ARG ARG ARG ARG ARG SER ALA ALA THR SER SER SER SER SER SER SER THR 117 PHE PHE LEU LEU LEU LEU PHE LEU PHE SER SER ILE THR THR THR THR SER SER SER SER 118 LEU LEU LEU LEU LEU LEU LEU LEU VAL GLU GLU ARG ARG ARG GLU GLU GLY GLY LEU VAL 119 ARG ARG ARG ARG ARG ARG ARG ARG ALA SER SER THR SER GLY GLY GLY ALA ALA PRO PRO 120 GLY GLY GLY GLY GLY GLY GLY GLY GLY PHE PHE PHE SER SER TYR TYR PHE PHE THR THR 121 TYR TYR TYR HIS TYR TYR TYR TYR TYR LEU LEU PHE GLN ARG TRP TRP TRP TRP ALA ALA 122 HIS HIS HIS ASP LEU GLN GLU GLU GLU HIS HIS ASP HIS HIS LYS LYS LYS LYS VAL LYS 123 GLN GLN GLN GLN GLN GLN GLN GLN GLY VAL VAL ILE PHE PHE TYR TYR TYR TYR PHE PHE 124 TYR TYR ASN SER PHE TYR PHE TYR PHE ALA ALA ALA TYR TYR GLY GLY TYR TYR ALA ALA 125 ALA ALA ALA ALA ALA ALA ALA ALA GLY PHE PHE TYR TYR TYR TYR TYR TYR TYR LEU LEU 126 TYR TYR TYR TYR TYR TYR TYR TYR TRP GLN GLN GLU ASP ASN ASP ASP ASP ASP ASN ASN 127 ASP ASP ASP ASP GLU ASP ASP ASP ASP GLY GLY GLY GLY GLY GLY GLY GLY GLY GLY GLY 128 GLY GLY GLY GLY GLY GLY GLY GLY GLY LYS LYS GLN GLU GLU GLN GLN LYS LYS GLU GLU 129 LYS LYS LYS LYS ARG CYS LYS LYS GLU TYR TYR ASN LEU LEU ASP ASP ASP ASP GLU GLU 130 ASP ASP ASP ASP ASP ASP ASP ASP THR VAL VAL PHE PHE PHE HIS HIS TYR TYR PHE PHE 131 TYR TYR TYR TYR TYR TYR TYR TYR LEU VAL VAL LEU LEU LEU LEU LEU ILE ILE MET MET 132 ILE ILE ILE ILE ILE ILE LEU LEU MET ARG ARG ARG SER SER GLU GLU GLU GLU ARG ASN 133 ALA ALA ALA ALA ALA ALA THR ALA GLU PHE PHE PHE GLN GLN PHE PHE PHE PHE PHE PHE 134 LEU LEU LEU LEU LEU LEU LEU LEU LEU TRP TRP ASN ASN ASN CYS CYS ASN ASN ASN ASP 135 LYS LYS ASN ASN ASN ASN ASN ASN LYS GLY GLY LEU LEU LEU PRO PRO LYS LYS PRO LEU 136 GLU GLU GLU GLU GLU GLU GLU GLU ASP THR THR ASP GLU GLU ASP ASP GLU GLU ARG LYS 137 ASP ASP ASP ASP ASP ASP ASP ASP ASN SER SER ALA THR THR THR THR ILE ILE THR GLN 138 LEU LEU LEU LEU LEU LEU LEU LEU LEU TRP TRP GLY LYS GLN LEU LEU PRO PRO GLY GLY 139 ARG ARG SER SER LYS LYS ARG ARG THR GLN GLN THR GLU GLU ASP ASP ALA ALA ASN THR 140 SER SER SER SER THR THR SER SER LEU THR THR TRP TRP SER TRP TRP TRP TRP TRP TRP 141 TRP TRP TRP TRP TRP TRP TRP TRP TRP VAL VAL ASP THR THR ARG ARG VAL VAL SER GLY 142 THR THR THR THR THR THR THR THR THR PRO PRO GLN MET VAL ALA ALA PRO PRO GLY GLY 143 ALA ALA ALA ALA ALA ALA ALA ALA GLY GLY GLY MET PRO PRO ALA ALA PHE PHE GLU ASP 144 ALA ALA ALA ALA ALA ALA VAL ALA PRO ALA ALA GLN GLN GLN GLU GLU ASP ASP TRP TRP 145 ASP ASP ASP ASP ASP ASP ASP ASP ASN PRO PRO HIS SER SER PRO PRO PRO PRO PRO PRO 146 MET MET THR THR MET MET THR THR TYR SER SER ASN SER SER ARG ARG ALA ALA GLU GLU S16

17 147 ALA ALA ALA ALA ALA ALA ALA ALA GLU TRP TRP GLN ARG ARG ALA ALA ALA ALA THR ALA 148 ALA ALA ALA ALA ALA ALA ALA ALA ILE LEU LEU LEU ALA ALA TRP TRP GLN GLN ASP LEU 149 SER 150 TRP 151 LEU 152 LYS 153 GLN GLN GLN 154 GLN THR THR 155 LYS LEU LEU 156 THR SER ALA ALA 157 TYR ASP ASP ALA MET MET 158 GLN GLN GLN GLN GLN LEU GLN GLN ILE LEU LEU LYS ASN ASN PRO PRO ILE ILE ILE ALA 159 THR THR ILE ILE ILE ILE ILE ILE ASP PRO PRO ALA VAL VAL THR THR THR THR VAL ILE 160 THR THR THR THR THR THR SER SER GLY ILE ILE GLU ARG THR LYS LYS LYS LYS GLY SER 161 LYS LYS GLN GLN ARG LYS GLU LYS LYS LYS LYS HIS ASN ASN LEU LEU GLN GLN ASN GLN 162 HIS HIS ARG ARG ARG HIS GLN ARG ILE VAL VAL LEU PHE PHE GLU GLU LYS LYS LEU ARG 163 LYS LYS LYS LYS LYS LYS LYS LYS LYS LEU LEU MET LEU TRP TRP TRP TRP TRP TRP TRP 164 TRP TRP TRP TRP TRP TRP SER CYS ASN ASN ASN ALA LYS LYS GLU GLU GLU GLU MET GLN 165 GLU GLU GLU GLU GLU GLU ASN GLU ILE ALA ALA ASN GLU GLU ARG ARG ALA ALA LYS GLN 166 ALA ALA ALA ALA GLN GLN ASP ALA SER ASP ASP ALA ASP ASP HIS HIS GLU GLU GLN GLN 167 ALA ALA ALA ALA SER ALA ALA ALA GLU GLN GLN SER ALA ALA LYS LYS PRO PRO PRO ASP 168 HIS HIS ARG ARG GLY GLY SER ASN GLY GLY GLY THR MET MET ILE ILE VAL VAL GLU LYS 169 VAL VAL VAL VAL ALA GLU GLU VAL ASP THR THR LEU LYS LYS ARG ARG TYR TYR ALA ALA 170 ALA ALA ALA ALA ALA ALA ALA ALA THR SER SER ASN THR THR ALA ALA VAL VAL ALA ALA 171 GLU GLU GLU GLU GLU GLU GLU GLU THR ALA ALA GLU LYS LYS ARG ARG GLN GLN ARG ASN 172 GLN GLN GLN GLN HIS ARG HIS GLN ILE THR THR VAL THR THR GLN GLN ARG ARG LYS LYS 173 LEU LEU LEU LEU TYR LEU GLN ARG GLN VAL VAL ILE HIS HIS ASN ASN ALA ALA GLU GLU 174 ARG ARG ARG ARG LYS ARG ARG ARG ARG GLN GLN GLN TYR TYR ARG ARG LYS LYS SER LEU 175 ALA ALA ALA ALA ALA ALA ALA ALA ASN MET MET VAL HIS ARG ALA ALA ALA ALA GLU THR 176 TYR TYR TYR TYR TYR TYR TYR TYR TYR LEU LEU LEU ALA ALA TYR TYR TYR TYR PHE PHE 177 LEU LEU LEU LEU LEU LEU LEU LEU LEU LEU LEU LEU MET MET LEU LEU LEU LEU LEU LEU 178 GLU GLU GLU GLU GLU GLU GLU GLU LYS ASN ASN ASN HIS GLN GLU GLU GLU GLU LEU LEU 179 GLY GLY GLY GLY GLY GLY ASP GLY GLY ASP ASP ASP ALA ALA ARG ARG GLU GLU THR PHE 180 THR THR GLU LEU GLU THR THR THR ASN THR THR THR ASP ASP ASP ASP GLU GLU SER SER 181 CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS 182 VAL VAL VAL VAL VAL VAL VAL VAL THR PRO PRO VAL LEU LEU PRO PRO PRO PRO PRO PRO 183 GLU GLU GLU GLU GLU GLU GLU GLU GLN LEU LEU ASP GLN GLN ALA ALA ALA ALA GLU HIS 184 TRP TRP TRP TRP TRP TRP TRP TRP TRP PHE PHE ILE GLU LYS GLN GLN THR THR ARG ARG 185 LEU LEU LEU LEU LEU LEU LEU LEU SER VAL VAL LEU LEU LEU LEU LEU LEU LEU LEU LEU 186 ARG ARG ARG ARG HIS ARG HIS HIS VAL ARG ARG ARG ARG GLN GLN GLN ARG ARG LEU ARG 187 ARG ARG ARG ARG ARG ARG LYS ARG ILE GLY GLY LEU ARG ARG GLN GLN LYS LYS GLY GLU 188 TYR TYR TYR TYR TYR TYR TYR TYR TYR LEU LEU PHE TYR TYR LEU LEU TYR TYR HIS HIS 189 LEU LEU LEU LEU LEU LEU LEU LEU SER LEU LEU ILE LEU LEU LEU LEU LEU LEU LEU LEU 190 GLU GLU GLU GLU LYS LYS GLU GLU GLY GLU GLU GLN LYS LYS GLU GLU LYS LYS GLU GLU 191 ASN ASN ASN ASN ASN ASN LYS ASN ALA ALA ALA SER SER LEU LEU TYR TYR ARG ARG 192 GLY GLY GLY GLY GLY GLY GLY GLY GLY GLY GLY GLY GLY GLY GLY SER SER GLY GLY 193 LYS LYS LYS LYS ASN ASN LYS LYS LYS LYS LYS VAL VAL ARG ARG LYS LYS ARG ARG 194 GLU GLU GLU GLU ALA ALA GLU GLU SER SER ALA VAL ALA GLY GLY ASN ASN GLN GLY 195 THR THR THR THR THR THR THR MET ASP ASP ASP LEU ILE VAL VAL ILE ILE ASN ASN 196 LEU LEU LEU LEU LEU LEU LEU LEU PHE LEU LEU LEU ARG ARG LEU LEU LEU LEU LEU LEU S17

18 197 GLN GLN GLN GLN LEU LEU LEU GLN GLN GLU GLU GLU ARG ARG ASP ASP ASP ASP GLU GLU 198 ARG ARG ARG ARG ARG ARG HIS ARG PRO LYS LYS ARG THR THR GLN GLN ARG ARG TRP TRP 199 THR THR ALA ALA THR THR LEU ALA PRO GLN GLN GLN VAL VAL GLN GLN GLN GLN LYS LYS 200 ASP ASP ASP ASP ASP ASP GLU ASP VAL GLU GLU VAL PRO PRO VAL VAL ASP ASP GLU GLU 201 ALA ALA PRO PRO SER SER PRO PRO THR LYS LYS PRO PRO PRO PRO PRO PRO PRO PRO PRO 202 PRO PRO PRO PRO PRO PRO PRO PRO HIS PRO PRO PRO MET MET PRO PRO PRO PRO PRO PRO 203 LYS LYS LYS LYS LYS LYS LYS LYS PRO VAL VAL MET VAL VAL LEU LEU SER SER SER SER 204 THR THR THR THR ALA ALA THR THR VAL ALA ALA ALA ASN ASN VAL VAL VAL VAL MET MET 205 HIS HIS HIS HIS HIS HIS HIS HIS VAL TRP TRP VAL VAL VAL LYS LYS VAL VAL ARG ARG 206 MET MET VAL VAL VAL VAL VAL VAL LYS LEU LEU VAL THR THR VAL VAL VAL VAL LEU LEU 207 THR THR THR THR THR THR THR THR GLY SER SER PHE ARG CYS THR THR THR THR LYS LYS 208 HIS HIS HIS HIS HIS HIS HIS HIS GLY SER SER ALA SER SER HIS HIS SER SER ALA ALA 209 HIS HIS HIS HIS HIS HIS HIS HIS VAL VAL VAL ARG GLU GLU HIS HIS HIS HIS ARG ARG 210 ALA ALA PRO PRO PRO SER PRO PRO ARG PRO PRO THR ALA VAL VAL VAL GLN GLN PRO PRO 211 VAL VAL ILE VAL ARG ARG ILE VAL ASN SER SER ALA SER SER THR THR ALA ALA GLY SER 212 SER SER SER SER SER PRO SER PHE GLN SER SER Xaa ASN SER 213 ASP ASP ASP ASP LYS GLU ASP ASP ASN ALA ALA Xaa PRO PRO SER PRO 214 HIS HIS HIS HIS GLY ASP HIS TYR ASP HIS HIS GLU GLU SER SER GLY GLY GLY GLY 215 GLU GLU GLU GLU GLU LYS GLU GLU ASN GLY GLY Xaa GLY GLY SER SER GLU GLU SER PHE 216 ARG HIS HIS GLN ASN ASN VAL VAL LYS LYS 217 ALA ALA ALA ALA VAL VAL ALA ALA ALA ARG ARG LEU ILE ILE THR THR LYS LYS SER SER 218 THR THR THR THR THR THR THR THR GLU GLN GLN LEU THR THR THR THR LYS LYS VAL VAL 219 LEU LEU LEU LEU LEU LEU LEU LEU ALA LEU LEU LEU VAL VAL LEU LEU LEU LEU LEU LEU 220 ARG ARG ARG ARG ARG ARG ARG ARG PHE VAL VAL VAL THR THR ARG ARG LYS LYS THR THR 221 CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS 222 TRP TRP TRP TRP TRP TRP TRP TRP THR HIS HIS ARG ARG ARG ARG ARG LEU LEU ALA SER 223 ALA ALA ALA ALA ALA ALA ALA ALA SER VAL VAL VAL ALA ALA ALA ALA ALA ALA ALA ALA 224 LEU LEU LEU LEU LEU LEU LEU LEU TYR SER SER THR SER SER LEU LEU TYR TYR PHE PHE 225 SER SER GLY GLY GLY GLY GLY GLY GLY GLY GLY SER GLY SER ASN ASN ASP ASP SER SER 226 PHE PHE PHE PHE PHE PHE PHE PHE PHE PHE PHE PHE PHE PHE TYR TYR PHE PHE PHE PHE 227 TYR TYR TYR TYR TYR TYR TYR TYR PHE TYR TYR TYR TYR TYR TYR TYR TYR TYR TYR TYR 228 PRO PRO PRO PRO PRO PRO PRO PRO PRO PRO PRO PRO PRO PRO PRO PRO PRO PRO PRO PRO 229 ALA ALA ALA ALA ALA ALA ALA ALA GLY LYS LYS ARG TRP ARG GLN GLN GLY GLY PRO PRO 230 GLU GLU GLU GLU ASP ASP GLU GLU GLU PRO PRO PRO ASN ASN ASN ASN LYS LYS GLU GLU 231 ILE ILE ILE ILE ILE ILE ILE ILE ILE VAL VAL ILE ILE ILE ILE ILE ILE ILE LEU LEU 232 THR THR THR THR THR THR THR ILE GLN TRP TRP ALA THR THR THR THR ASP ASP LYS GLN 233 LEU LEU LEU LEU LEU LEU LEU LEU ILE VAL VAL VAL LEU LEU MET MET VAL VAL PHE LEU 234 THR THR THR THR THR THR THR THR THR MET MET THR SER THR LYS LYS HIS HIS ARG ARG 235 TRP TRP TRP TRP TRP TRP TRP TRP PHE TRP TRP TRP TRP TRP TRP TRP TRP TRP PHE PHE 236 GLN GLN GLN GLN GLN GLN GLN GLN ILE MET MET LEU ARG ARG LEU LEU THR THR LEU LEU 237 ARG ARG ARG ARG LEU LEU GLN ARG HIS ARG ARG ARG GLN GLN LYS LYS ARG ARG ARG ARG 238 ASP ASP ASP ASP ASN ASN ASP ASP TYR GLY GLY ASP ASP ASP ASP ASP ALA ALA ASN ASN 239 GLY GLY GLY GLY GLY GLY GLY GLY GLY ASP ASP GLY GLY GLY LYS LYS GLY GLY GLY GLY 240 GLU GLU GLU GLU GLU GLU GLU GLU ASP GLN GLN ARG VAL VAL GLN GLN GLU GLU LEU LEU 241 ASP ASP ASP ASP GLU GLU GLY ASP LYS GLU GLU GLU SER SER PRO PRO VAL VAL ALA ALA 242 GLN GLN GLN GLN LEU LEU HIS GLN VAL GLN GLN VAL LEU LEU MET MET GLN GLN SER ALA 243 THR THR THR THR THR ILE THR THR PRO GLN GLN PRO SER SER ASP ASP GLU GLU GLY GLY 244 GLN GLN GLN GLN GLN GLN GLN GLN GLU GLY GLY PRO HIS HIS ALA ALA PRO PRO SER THR 245 ASP ASP ASP ASP ASP ASP ASP ASP ASP THR THR SER ASP ASN LYS LYS GLU GLU GLY GLY 246 THR THR THR THR MET MET THR VAL SER HIS HIS PRO THR THR GLU GLU LEU LEU ASN GLN 247 GLU GLU GLU GLU GLU GLU GLU GLU GLU ARG ARG ALA GLN GLN PHE PHE ARG ARG CYS GLY S18

19 248 LEU LEU LEU LEU LEU LEU LEU LEU PRO GLY GLY LEU GLN GLN GLU GLU GLY GLY SER ASP 249 VAL VAL VAL VAL VAL VAL VAL VAL GLN ASP ASP SER TRP TRP PRO PRO ASP ASP THR PHE 250 CYS PHE PHE THR GLY GLY LYS LYS VAL VAL 251 GLU GLU GLU GLU GLU GLU GLU GLU ASN LEU LEU GLY ASP ASP ASP ASP LEU LEU 252 THR THR THR THR THR THR THR THR PRO PRO PRO THR VAL VAL VAL VAL HIS HIS 253 ARG ARG ARG ARG ARG ARG ARG ARG LEU ASN ASN VAL LEU LEU LEU LEU ASN ASN GLY GLY 254 PRO PRO PRO PRO PRO PRO PRO PRO LEU ALA ALA LEU PRO PRO PRO PRO GLY GLY PRO PRO 255 ALA ALA ALA ALA ALA ALA ALA ALA PRO ASP ASP PRO ASP ASP ASN ASN ASN ASN ASN ASN 256 GLY GLY GLY GLY GLY GLY GLY GLY THR GLU GLU ASN GLY GLY GLY GLY GLY GLY GLY SER 257 ASP ASP ASP ASP ASP ASP ASP ASP LEU THR THR ALA ASN ASN ASP ASP THR THR ASP ASP 258 GLY GLY ARG ARG GLY GLY GLY GLY ASP TRP TRP ASP GLY GLY GLY GLY TYR TYR GLY GLY 259 THR THR THR THR THR THR THR THR GLY TYR TYR LEU THR THR THR THR GLN GLN SER SER 260 PHE PHE PHE PHE PHE PHE PHE PHE THR LEU LEU THR TYR TYR TYR TYR SER SER PHE PHE 261 GLN GLN GLN GLN GLN GLN GLN GLN PHE GLN GLN TYR GLN GLN GLN GLN TRP TRP HIS HIS 262 LYS LYS LYS LYS LYS LYS LYS LYS HIS ALA ALA GLN THR THR GLY GLY VAL VAL ALA ALA 263 TRP TRP TRP TRP TRP TRP TRP TRP GLN THR THR LEU TRP TRP TRP TRP VAL VAL TRP SER 264 ALA ALA ALA ALA ALA ALA ALA ALA GLY LEU LEU ARG VAL VAL ILE ILE VAL VAL SER SER 265 ALA ALA ALA ALA SER SER ALA ALA ASP ASP SER ALA ALA THR THR ALA ALA LEU SER 266 THR 267 VAL VAL VAL VAL VAL VAL VAL VAL CYS LEU THR THR LEU LEU LEU LEU 268 VAL VAL VAL VAL VAL VAL VAL VAL TYR LEU ARG ARG ALA ALA GLU THR 269 VAL VAL VAL VAL VAL VAL VAL VAL VAL VAL VAL VAL ILE ILE VAL VAL VAL VAL VAL VAL 270 PRO PRO PRO PRO PRO PRO PRO PRO ALA GLU GLU SER CYS ARG PRO PRO PRO PRO LYS LYS 271 SER SER SER SER LEU LEU SER SER ILE ALA ALA PRO GLN GLN PRO PRO PRO PRO ARG SER 272 GLY GLY GLY GLY GLY GLY GLY GLY PHE GLY GLY Xaa GLY GLY GLY GLY GLN GLN GLY GLY 273 GLN GLN GLU GLU LYS LYS GLU GLU SER GLU GLU Xaa GLU GLU GLU GLU ASP ASP ASP ASP 274 GLU GLU GLU GLU GLU GLU GLU GLU ASN GLU GLU Xaa GLU GLU GLU GLU THR THR GLU GLU 275 GLN GLN GLN GLN GLN GLN GLN GLN GLN ALA ALA HIS GLN GLN GLN GLN ALA ALA HIS HIS 276 ARG ARG ARG ARG ASN TYR ARG ARG ASN GLY GLY GLY ARG ARG ARG ARG PRO PRO HIS HIS 277 TYR TYR TYR TYR TYR TYR TYR TYR TYR LEU LEU TYR PHE PHE TYR TYR TYR TYR TYR TYR 278 THR THR THR THR THR THR THR THR THR ALA ALA ALA THR THR THR THR SER SER GLN CYS 279 CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS CYS 280 HIS HIS HIS HIS ARG HIS HIS HIS ARG ARG ARG ARG TYR TYR GLN GLN HIS HIS GLN ILE 281 VAL VAL VAL VAL VAL VAL VAL VAL VAL VAL VAL VAL MET MET VAL VAL VAL VAL VAL VAL 282 GLN GLN GLN GLN TYR TYR GLN GLN THR LYS LYS GLN GLU GLU GLU GLU GLN GLN GLU GLN 283 HIS HIS HIS HIS HIS HIS HIS HIS HIS HIS HIS HIS HIS HIS HIS HIS HIS HIS HIS HIS 284 GLU GLU GLU GLU GLU GLN GLU GLU GLY SER SER CYS SER SER PRO PRO SER SER GLU ALA 285 GLY GLY GLY GLY GLY GLY GLY GLY ASN SER SER SER GLY GLY GLY GLY SER SER GLY GLY 286 LEU LEU LEU LEU LEU LEU LEU LEU TRP LEU LEU LEU ASN ASN LEU LEU LEU LEU LEU LEU 287 PRO PRO PRO PRO PRO PRO PRO PRO THR GLY GLY GLY HIS HIS ASP ASP ALA ALA ALA ALA 288 LYS LYS LYS LYS GLU GLU GLU GLU VAL GLY GLY Xaa SER GLY GLN GLN GLN GLN GLN GLN 289 PRO PRO PRO PRO PRO PRO PRO PRO GLU GLN GLN ARG THR THR PRO PRO PRO PRO PRO PRO 290 LEU LEU LEU LEU LEU LEU VAL LEU ILE ASP ASP SER HIS HIS LEU LEU LEU LEU LEU LEU 291 THR THR THR THR THR THR THR MET PRO ILE ILE LEU PRO PRO ILE ILE VAL VAL THR ARG 292 LEU LEU LEU LEU LEU LEU LEU LEU ILE ILE ILE LEU VAL VAL VAL VAL VAL VAL VAL VAL 293 ARG ARG ARG ARG ARG ARG ARG ARG SER LEU LEU VAL PRO PRO ILE ILE PRO PRO ASP GLU 294 TRP TRP TRP TRP TRP TRP TRP TRP VAL TYR TYR PRO SER SER TRP TRP TRP TRP LEU LEU 295 GLU GLU GLU GLU GLU LYS THR TRP TRP TRP GLU GLU 296 PRO PRO PRO PRO PRO GLN HIS ALA ALA 297 S19

20 Table S5. Quantification of supersecondary structure homology of light chain of immunoglobulin (2w9e: mouse) 14 between subunits of proteins (516 subunits) and between fragments. 8 Data mining of fragment homology using the combination of α-helix-type and β- sheet-type patterns extracted the correlation between fragments of light chain of immunoglobulin, MHC class I, MHC class II, and ZAG. PDBID Protein Subunit Fragment Homology Homology 2w9eL Immunogloblin (light chain) cd1B β-2microglobulin a6tA Immunogloblin (light chain) kykL Immunogloblin (light chain) i9rL Immunogloblin (light chain) d6eB HLA-DR4 BETA ianB HLAclassII(β) d5mB HLA-DR4 BETA u3hD H-2AclassII(β) bsrA HLAclassI(α) d6eA HLA-DR4 ALPHA cikA HLAclassI(α) e27A HLAclassI(α) t7vA ZAG t80A ZAG wbyA MHCclassI t7wA ZAG aqdB HLAclassII wbxA MHCclassI q6wB HLAclassII(β) dlhB HLAclassII(β) ogaA HLAclassI(α) bnqA HLAclassI(α) vlrA HLAclassI(α) t5wB HLAclassII(β) r5iB HLAclassII(β) dypA HLA G ANTIGEN kn2L Abzyme (light chain) e8L Immunogloblin (light chain) deeA IGM RF 2A2 (light chain) oslL Immunogloblin (light chain) bkyL Immunogloblin (light chain) eotL Immunogloblin (light chain) dn0A IGM-KAPPA COLD AGGLUTININ (light chain) qlrA IGM KAPPA CHAIN V-III yjdL Immunogloblin (light chain) hezA KAPPA LIGHT CHAIN OF IG mhpL Immunogloblin (light chain) eoaL Immunogloblin (light chain) drtA Immunogloblin (light chain) hc0L Immunogloblin (light chain) w9dL Immunogloblin (light chain) fgwL Immunogloblin (light chain) agjL YVO FAB, LIGHT CHAIN c5bL Abzyme (light chain) mcpL Immunogloblin (light chain) ao7A HLA-A a6zB β-2microglobulin haeL Immunogloblin (light chain) S20

21 2po6D NKT15(β) m1bB β-2microglobulin exuB β-2microglobulin bx8A LCN adqA IGG4 REA FC a7oL Immunogloblin (light chain) bnqE TRBC bk9A PBP ianE CD4+ T CELL RECEPTOR E8 BETA CHAIN adqL Immunogloblin (light chain) vlrE TCR BETA CHAIN ja4A CD w80A ALPHA-ADAPTIN C je6A MIC-B gmrA CD1D kcgC ULBP iy2A Immunogloblin (light chain) e3vA CD drtB Immunogloblin (heavy chain) m1bA FcRn gw5A ILT bd2E T CELL RECEPTOR BETA n5oX BRCA a3bB LUMAZINE PROTEIN hc0H Immunogloblin (heavy chain) ao7D T CELL RECEPTOR ALPHA p7qB β-2microglobulin u3hC H-2classII(α) mpuA NKG2-D imm Immunogloblin (light chain) wllA KIRBAC lnuB H-2AclassII(β) vdgA ILT u3hB MOUSE TCRVBETA cd1A CD i1aA FcRn gmlA CD1D gmnA CD1D b7fA SXL-LETHAL PROTEIN dypD ILT x4oA HLAclassI(α) jvgA CD1A tcrB TCR ddyA LUMAZINE PROTEIN aonO GROEL/GROES COMPLEX o9kA Rb o9kB Rb eoaH Immunogloblin (heavy chain) ianA HLAclassII(α) m1qA STCC o9kG Rb a6tB Immunogloblin (heavy chain) c8kA MHCclassI m17A FcRn alyA CD40-L p4lA MHCclassI dl2A KIR epfA NCAM p7qD LIR lnuA H-2classII(α) gssA GSTP frtC IGG FC g3yA GEM eotH Immunogloblin (heavy chain) vxsA CTLA mhpA CD49A ja3A LY49I vj0A ALPHA-ADAPTIN C wy3A MIC-B im9D KIR2DL S21

22 2ve6A MHCclassI bkyH Immunogloblin (heavy chain) e4kC CD qo3C LY49A wy3B UL xiwB CD bdwB CD159A jf1A FILAMIN-A p26A CD dn0B IGM-KAPPA COLD AGGLUTININ (heavy chain) lw2A PAI de4A HFE ckbH MHCclassI t89A IGG1-FC fruA FcRn ottX CD cadA LY49G i8iA DSFV MR p28B CD vxuL Immunogloblin (light chain) gt0C OTF d5oF IGG FC RECEPTOR II-A exuA FcRn t83C CD16-B dr9A CD g0xA ILT tcrA TCR hyrC MIC-A m1rA STCC kykH Immunogloblin (heavy chain) atnD DEOXYRIBONUCLEASE I j6eH IGM (heavy chain) fgwH Immunogloblin (heavy chain) dbxA CD qa9B CD mq8A CD i85C CTLA e4kA IGG1-FC kn2H Abzyme (heavy chain) ao7E T CELL RECEPTOR BETA gjiA C-REL PROTEIN d2uD ILT bd2D T CELL RECEPTOR ALPHA fikA CD1D bnqD TRAV hezB HEAVY CHAIN OF IG ciiH CD159A mtrA NCAM papA PAPAIN ogaE TRBC b6uA KIR2DL jffB Tublin(β) alcA α-lactalbumin b2xA CD49A gzmA Rhodopsin f1mA ACRA wh1Y RF aqdA HLAclassII d5mA HLA-DR4 ALPHA sebA HLAclassII t5wA HLAclassII(α) t83A IGG1-FC cjwA GEM ckbL β-2microglobulin khmB Fibroin qksA KIR ve6C SENDAI VIRUS EPITOPE cdgK CD159A e8H Immunogloblin (heavy chain) vlrD TCR ALPHA CHAIN S22

23 1bbt4 Foot-and-Mouth Disease Virus (Subunit VP4) ij9A VCAM-D1, f0bA GREEN FLUORESCENT PROTEIN p4lD LY49-C u3hA T-CELL RECEPTOR ALPHA-CHAIN wsoA GREEN FLUORESCENT PROTEIN nykA M dliA KIR2DL bbt2 Foot-and-Mouth Disease Virus (Subunit VP2) ckbA T CELL ANTIGEN RECEPTOR agjH YVO FAB, HEAVY CHAIN p28A CD ogaD TRAV gmrB β-2microglobulin vxuH Immunogloblin (heavy chain) bd2A HLA-A dlhA HLAclassII(α) i9rH Immunogloblin (heavy chain) mcpH Immunogloblin (heavy chain) p53A CD po6B β-2microglobulin i1aC WTFC ihwA AGAP deeB IGM RF 2A2 (heavy chain) fpuA EVASIN g9wA TALIN mj7B MCAR j6eL IGM (light chain) nkrA KIR2DL w9dH Immunogloblin (heavy chain) efxD KIR2DL qz1A LACTOFERRIN frtA FcRn z7zI CD g60A MCG d2uH ILT sy6A CD qlrB IGM FAB REGION IV-J(H4)-C r5iA HLAclassII(α) sebB HLAclassII ciiA MHCclassI e20A SUP c5bH Abzyme (heavy chain) yjdH Immunogloblin (heavy chain) orvA THYMIDINE KINASE qq0A THYMIDINE KINASE ut9A CBHA bkvB T u4rA CCL b7tY MYOSIN REGULATORY LIGHT CHAIN khmA Fibroin b6eA CD v7pB EMS16B xiwA CD dypB β-2microglobulin g61A MCG efuA EF-TU a7oH Immunogloblin (heavy chain) wsnA GREEN FLUORESCENT PROTEIN bbt1 Foot-and-Mouth Disease Virus (Subunit VP1) po6C NKT15(α) a6zA HFE ciiA HLAclassI(α) akjB β-2microglobulin cdgB β-2microglobulin ygrC ITAM haeH Immunogloblin (heavy chain) mj6A MCREA ufuA ILT c8kB β-2microglobulin S23

24 1qz1A NCAM zfrH Thrombin vscA VCAM adqH Immunogloblin (heavy chain) d2uE UL18 PROTEIN i8kA DSFV MR h8nA CD i85A B wahA IGG1 FC c8jA LY49C ckbB T CELL ANTIGEN RECEPTOR otpA ILT fjtA IG GAMMA h1lM P etsH Thrombin emsB CD i8lA B i9rA CD40-L kcgB NKG2-D st1A SUBTILISIN BPN' cdgA HLAclassI(α) hq8A NKG2-D kcgA NKG2-D p4lB β-2microglobulin sebD ENTEROTOXIN TYPE B druA CD w9eH Immunogloblin (heavy chain) gmlB β-2microglobulin gmnB β-2microglobulin imiA GST i1cA IGG2A jfmA RAE-1 BETA c7uA HLAclassI(α) sicI SSI btrA PTAC bkvA T fhtA VMIP-II hazA NCAM aipA EF-TU aorA Aldehyde Ferredoxin Oxidoreductase eqgA COX vcaA VCAM-D1, w7sA GREEN FLUORESCENT PROTEIN ihrs RF wbyB β-2microglobulin bnqB β-2microglobulin fikB β-2microglobulin ve6B β-2microglobulin d2uB β-2microglobulin dbxB β-2microglobulin qscA TRAF bj3B IX-BP waeA PBP bdwA CD akjA HLA-A po6A CD1D mj7A MCREA bd2B β-2microglobulin e27B β-2microglobulin frtB β-2microglobulin wbxB β-2microglobulin bsrB β-2microglobulin bvoB β-2microglobulin bzeB β-2microglobulin d2uF β-2microglobulin fruB β-2microglobulin kbxA CCL kbxB CCL bl8A POTASSIUM CHANNEL PROTEIN bl8B POTASSIUM CHANNEL PROTEIN S24

25 1de4B β-2microglobulin i1aB β-2microglobulin jvgC β-2microglobulin gstA RAT GST yojA Proto-Oncogene Tyrosine-Protein Kinase SRC ao7B β-2microglobulin bj3A IX-BP i8lC CTLA iamA CD yguC POLYOMA MIDDLE T ANTIGEN x0wA P ct7A ISOMERASE ctlA ISOMERASE ianD CD4+ T CELL RECEPTOR E8 ALPHA CHAIN k72A CD11 LIKE bbt3 Foot-and-Mouth Disease Virus (Subunit VP3) hnfA CD h6eA AP o9kP E2F o9kQ E2F emtC PSGL k71A CD11 LIKE b89A CLATHRIN HEAVY CHAIN tfeA EF-TS aipC EF-TS wrnZ EF-Tu wrqZ EF-Tu es6B SABP hyrB NKG2-D p1zD LY49-C ANTIGEN yguA CD i8kB DSFV MR lqvA EPCR ygrA CD bvoA HLAclassI(α) i8iB DSFV MR l8jA EPCR qa9A CD dmmD CD oslH Immunogloblin (heavy chain) vb1A Lysozyme C bzeA HLAclassI(α) p7qA HLA-A akjD CD e4jA CD yjdC CD dmmC CD zagA ZAG r5nA SUP onjA Sav ol0A Immunoglobulin G ol0B Immunoglobulin G bq4A CYTOCHROME C de4C Transferrin receptor k72B CD vk0B insulin (B chain) sicE SUBTILISIN BPN' k71B CD x44D CTLA bkvC T gt0D SOX cczA CD q3aA CD eoaI LFA-1A gqeA RF clcA ENDOGLUCANASE hezE PROTEIN L b7tZ MYOSIN ESSENTIAL LIGHT CHAIN rpxA 3-EPIMERASE tqxA 3-EPIMERASE S25

26 1kzzA CD40BP jbfA PBP b7tA MYOSIN HEAVY CHAIN ciiB β-2microglobulin cikB β-2microglobulin orqA MAC-NOS srvA GroEL(HSP60 class) h15B HLAclassII(β) o9kH Rb bx7A LCN xb2B EF-TS d4cA FCFR g9mC CD wbxC Influenza A peptide wbyC INFLUENZA A PEPTIDE pbjA mpges i1aD NBFC jl4D CD vkxA CD bd2C TAX PEPTIDE h6eP CTLA gc1C CD v7pC CD49B d2uA UL18 PROTEIN oslP CD dqtA CTLA vkwA CD g8kA LY49L capA Rhodopsin jffA Tublin(α) mhpX Immunogloblin (heavy chain) btrB Androgen receptor mhpH Immunogloblin (heavy chain) xb2A EF-TU hcsB HUMAN SRC c8kD LY-49C atnA ACTIN i4m Prion vk0A insulin (A chain) t89C CD16-B vcqA H-PGDS vczA H-PGDS bx7C CTLA k0kA BRCA aonA GROEL g9wC VLA wgpA MKP ctkA RIP fpuB C-C MOTIF CHEMOKINE h1lA LARGE T ANTIGEN a1rA NS3 PROTEIN d00A TRAF efuB EF-TS hyrA NKG2-D m4kA KIR2DS cm9A VMIP-II dolA MCP j6eA IGG g8lB LY49L bimA P pttA CD pttB CD agpA EF-TS es6A ZAG mq8B CD11A ogaB β-2microglobulin c7uB β-2microglobulin vlrB β-2microglobulin x4oB β-2microglobulin ciiB β-2microglobulin S26

27 3m17B β-2microglobulin bxgA HAS a0oA CHEY icaA CD11A kidA GroEL(HSP60 class) lfaA CD11A ncnA CD pt6A CD49A r5iD SUPERANTIGEN bhmA BAMHI bhmB BAMHI cqpA CD11A ciiG CD m1pA STCC v7pA EMS16A cdgJ CD iy2B Immunogloblin (heavy chain) ssiA SSI h15A HLAclassII(α) q6wA HLAclassII(α) dlhC ENTEROTOXIN TYPE B PRECURSOR r5iC HEMAGGLUTININ PEPTIDE u3hP MYELIN BASIC PROTEIN (MBP)-PEPTIDE bsrC EPSTEIN-BARR NUCLEAR ANTIGEN c7uC GAG PROTEIN cikC PEPTIDE EPITOPE dypC 9 MER PEPTIDE FROM HISTONE H2A.X ianC 15-MER Peptide from Triosephosphate Isomerase jf1T CD vlrC FLU MATRIX PEPTIDE zpyB CD bzeP HLA G ANTIGEN d2uC ACTIN d2uG ACTIN zpyA ESP a1rC NS4A PROTEIN deeG Ig G Binding Protein A bvoC GAG PROTEIN ckbP DEV8 PEPTIDE vj0P SYNAPTOJANIN emsA ESP bkyP CD w9eA Prion a0oB CHEA ptuA CD agqA EF-TS emtA ESP S27

28 Figure S1. Interaction of CD4 with MHC class II (1jl4: human). 21 CD4 (red) did not contact with both of the conformational fragments (string shhshss ) in α-chain (blue) and β-chain (green) of MHC class II. S28

29 Figure S2. Interaction of CD8 with MHC class I (1akj: human). 22 CD8 (red) did not contact with both of the conformational fragments (string shhshss ) in α-chain (blue) and β-2 microglobulin (green) of MHC class I. S29

30 Figure S3. Interaction of KIR with MHC class I (1efx: human). 23 KIR (red) did not contact with both of the conformational fragments (string shhshss ) in α-chain (blue) and β-2 microglobulin (green) of MHC class I. S30

31 Figure S4. Interaction of LILR with β-2 microglobulin (3d2u: human). 25 The unchanging conformational fragment (red: string sohsss ) of main chain in LILR connected with the conformational fragment (blue: string shhshss ) in β-2 microglobulin as a type of pair forms. S31