5fa4

Structural highlights

Disease

HLAA_HUMAN Selection of immunotherapy in solid cancer;Birdshot chorioretinopathy;Prediction of phenytoin or carbamazepine toxicity. Alleles A*02:01 and A*24:02 are associated with increased susceptibility to diabetes mellitus, insulin-dependent (IDDM) (PubMed:22245737, PubMed:18802479, PubMed:16731854, PubMed:22522618). In a glucose-dependent way, allele A*02:01 may aberrantly present the signal peptide of preproinsulin (ALWGPDPAAA) on the surface of pancreatic beta cells to autoreactive CD8-positive T cells, potentially driving T-cell mediated cytotoxicity in pancreatic islets (PubMed:22245737, PubMed:18802479). Allele A*24:02 may present the signal peptide of preproinsulin (LWMRLLPLL) and contribute to acute pancreatic beta-cell destruction and early onset of IDDM (PubMed:16731854, PubMed:22522618).^{[1] [2] [3] [4]} Allele A*03:01 is associated with increased susceptibility to multiple sclerosis (MS), an autoimmune disease of the central nervous system (PubMed:10746785). May contribute to the initiation phase of the disease by presenting myelin PLP1 self-peptide (KLIETYFSK) to autoreactive CD8-positive T cells capable of initiating the first autoimmune attacks (PubMed:18953350).^{[5] [6]} Allele A*26:01 is associated with increased susceptibility to Behcet disease (BD) in the Northeast Asian population. Especially in the HLA-B*51-negative BD populations, HLA-A*26 is significantly associated with the onset of BD.^[7] Allele A*29:02 is associated with increased susceptibility to birdshot chorioretinopathy (BSCR). May aberrantly present retinal autoantigens and induce autoimmune uveitis.^[8]

Function

HLAA_HUMAN Antigen-presenting major histocompatibility complex class I (MHCI) molecule. In complex with B2M/beta 2 microglobulin displays primarily viral and tumor-derived peptides on antigen-presenting cells for recognition by alpha-beta T cell receptor (TCR) on HLA-A-restricted CD8-positive T cells, guiding antigen-specific T cell immune response to eliminate infected or transformed cells (PubMed:2456340, PubMed:2784196, PubMed:1402688, PubMed:7504010, PubMed:9862734, PubMed:10449296, PubMed:12138174, PubMed:12393434, PubMed:15893615, PubMed:17189421, PubMed:19543285, PubMed:21498667, PubMed:24192765, PubMed:7694806, PubMed:24395804, PubMed:28250417). May also present self-peptides derived from the signal sequence of secreted or membrane proteins, although T cells specific for these peptides are usually inactivated to prevent autoreactivity (PubMed:25880248, PubMed:7506728, PubMed:7679507). Both the peptide and the MHC molecule are recognized by TCR, the peptide is responsible for the fine specificity of antigen recognition and MHC residues account for the MHC restriction of T cells (PubMed:12796775, PubMed:18275829, PubMed:19542454, PubMed:28250417). Typically presents intracellular peptide antigens of 8 to 13 amino acids that arise from cytosolic proteolysis via IFNG-induced immunoproteasome or via endopeptidase IDE/insulin-degrading enzyme (PubMed:17189421, PubMed:20364150, PubMed:17079320, PubMed:26929325, PubMed:27049119). Can bind different peptides containing allele-specific binding motifs, which are mainly defined by anchor residues at position 2 and 9 (PubMed:7504010, PubMed:9862734).^{[9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] [31] [32] [33] [34]} Allele A*01:01: Presents a restricted peptide repertoire including viral epitopes derived from IAV NP/nucleoprotein (CTELKLSDY), IAV PB1/polymerase basic protein 1 (VSDGGPNLY), HAdV-11 capsid L3/hexon protein (LTDLGQNLLY), SARS-CoV-2 3a/ORF3a (FTSDYYQLY) as well as tumor peptide antigens including MAGE1 (EADPTGHSY), MAGEA3 (EVDPIGHLY) and WT1 (TSEKRPFMCAY), all having in common a canonical motif with a negatively charged Asp or Glu residue at position 3 and a Tyr anchor residue at the C-terminus (PubMed:1402688, PubMed:7504010, PubMed:17189421, PubMed:20364150, PubMed:25880248, PubMed:30530481, PubMed:19177349, PubMed:24395804, PubMed:26758806, PubMed:32887977). A number of HLA-A*01:01-restricted peptides carry a post-translational modification with oxidation and N-terminal acetylation being the most frequent (PubMed:25880248). Fails to present highly immunogenic peptides from the EBV latent antigens (PubMed:18779413).^{[35] [36] [37] [38] [39] [40] [41] [42] [43] [44]} Allele A*02:01: A major allele in human populations, presents immunodominant viral epitopes derived from IAV M/matrix protein 1 (GILGFVFTL), HIV-1 env (TLTSCNTSV), HIV-1 gag-pol (ILKEPVHGV), HTLV-1 Tax (LLFGYPVYV), HBV C/core antigen (FLPSDFFPS), HCMV UL83/pp65 (NLVPMVATV) as well as tumor peptide antigens including MAGEA4 (GVYDGREHTV), WT1 (RMFPNAPYL) and CTAG1A/NY-ESO-1 (SLLMWITQC), all having in common hydrophobic amino acids at position 2 and at the C-terminal anchors.^{[45] [46] [47] [48] [49] [50] [51] [52] [53] [54] [55] [56] [57] [58] [59] [60] [61]} Allele A*03:01: Presents viral epitopes derived from IAV NP (ILRGSVAHK), HIV-1 nef (QVPLRPMTYK), HIV-1 gag-pol (AIFQSSMTK), SARS-CoV-2 N/nucleoprotein (KTFPPTEPK) as well as tumor peptide antigens including PMEL (LIYRRRLMK), NODAL (HAYIQSLLK), TRP-2 (RMYNMVPFF), all having in common hydrophobic amino acids at position 2 and Lys or Arg anchor residues at the C-terminus (PubMed:7504010, PubMed:7679507, PubMed:9862734, PubMed:19543285, PubMed:21943705, PubMed:2456340, PubMed:32887977). May also display spliced peptides resulting from the ligation of two separate proteasomal cleavage products that are not contiguous in the parental protein (PubMed:27049119).^{[62] [63] [64] [65] [66] [67] [68]} Allele A*11:01: Presents several immunodominant epitopes derived from HIV-1 gag-pol and HHV-4 EBNA4, containing the peptide motif with Val, Ile, Thr, Leu, Tyr or Phe at position 2 and Lys anchor residue at the C-terminus. Important in the control of HIV-1, EBV and HBV infections (PubMed:10449296). Presents an immunodominant epitope derived from SARS-CoV-2 N/nucleoprotein (KTFPPTEPK) (PubMed:32887977).^{[69] [70]} Allele A*23:01: Interacts with natural killer (NK) cell receptor KIR3DL1 and may contribute to functional maturation of NK cells and self-nonself discrimination during innate immune response.^[71] Allele A*24:02: Presents viral epitopes derived from HIV-1 nef (RYPLTFGWCF), EBV lytic- and latent-cycle antigens BRLF1 (TYPVLEEMF), BMLF1 (DYNFVKQLF) and LMP2 (IYVLVMLVL), SARS-CoV nucleocapsid/N (QFKDNVILL), as well as tumor peptide antigens including PRAME (LYVDSLFFL), all sharing a common signature motif, namely an aromatic residue Tyr or Phe at position 2 and a nonhydrophobic anchor residue Phe, Leu or Iso at the C-terminus (PubMed:9047241, PubMed:12393434, PubMed:24192765, PubMed:20844028). Interacts with natural killer (NK) cell receptor KIR3DL1 and may contribute to functional maturation of NK cells and self-nonself discrimination during innate immune response (PubMed:17182537, PubMed:18502829).^{[72] [73] [74] [75] [76] [77]} Allele A*26:01: Presents several epitopes derived from HIV-1 gag-pol (EVIPMFSAL, ETKLGKAGY) and env (LVSDGGPNLY), carrying as anchor residues preferentially Glu at position 1, Val or Thr at position 2 and Tyr at the C-terminus.^[78] Allele A*29:02: Presents peptides having a common motif, namely a Glu residue at position 2 and Tyr or Leu anchor residues at the C-terminus.^[79] Allele A*32:01: Interacts with natural killer (NK) cell receptor KIR3DL1 and may contribute to functional maturation of NK cells and self-nonself discrimination during innate immune response.^[80] Allele A*68:01: Presents viral epitopes derived from IAV NP (KTGGPIYKR) and HIV-1 tat (ITKGLGISYGR), having a common signature motif namely, Val or Thr at position 2 and positively charged residues Arg or Lys at the C-terminal anchor.^{[81] [82] [83]} Allele A*74:01: Presents immunodominant HIV-1 epitopes derived from gag-pol (GQMVHQAISPR, QIYPGIKVR) and rev (RQIHSISER), carrying an aliphatic residue at position 2 and Arg anchor residue at the C-terminus. May contribute to viral load control in chronic HIV-1 infection.^[84]

See Also

• Beta-2 microglobulin 3D structures

References

1. ↑ Nakanishi K, Inoko H. Combination of HLA-A24, -DQA1*03, and -DR9 contributes to acute-onset and early complete beta-cell destruction in type 1 diabetes: longitudinal study of residual beta-cell function. Diabetes. 2006 Jun;55(6):1862-8. doi: 10.2337/db05-1049. PMID:16731854 doi:http://dx.doi.org/10.2337/db05-1049
2. ↑ Skowera A, Ellis RJ, Varela-Calvino R, Arif S, Huang GC, Van-Krinks C, Zaremba A, Rackham C, Allen JS, Tree TI, Zhao M, Dayan CM, Sewell AK, Unger WW, Drijfhout JW, Ossendorp F, Roep BO, Peakman M. CTLs are targeted to kill beta cells in patients with type 1 diabetes through recognition of a glucose-regulated preproinsulin epitope. J Clin Invest. 2008 Oct;118(10):3390-402. doi: 10.1172/JCI35449. PMID:18802479 doi:http://dx.doi.org/10.1172/JCI35449
3. ↑ Bulek AM, Cole DK, Skowera A, Dolton G, Gras S, Madura F, Fuller A, Miles JJ, Gostick E, Price DA, Drijfhout JW, Knight RR, Huang GC, Lissin N, Molloy PE, Wooldridge L, Jakobsen BK, Rossjohn J, Peakman M, Rizkallah PJ, Sewell AK. Structural basis for the killing of human beta cells by CD8(+) T cells in type 1 diabetes. Nat Immunol. 2012 Jan 15. doi: 10.1038/ni.2206. PMID:22245737 doi:10.1038/ni.2206
4. ↑ Kronenberg D, Knight RR, Estorninho M, Ellis RJ, Kester MG, de Ru A, Eichmann M, Huang GC, Powrie J, Dayan CM, Skowera A, van Veelen PA, Peakman M. Circulating preproinsulin signal peptide-specific CD8 T cells restricted by the susceptibility molecule HLA-A24 are expanded at onset of type 1 diabetes and kill beta-cells. Diabetes. 2012 Jul;61(7):1752-9. doi: 10.2337/db11-1520. Epub 2012 Apr 20. PMID:22522618 doi:http://dx.doi.org/10.2337/db11-1520
5. ↑ Fogdell-Hahn A, Ligers A, Gronning M, Hillert J, Olerup O. Multiple sclerosis: a modifying influence of HLA class I genes in an HLA class II associated autoimmune disease. Tissue Antigens. 2000 Feb;55(2):140-8. doi: 10.1034/j.1399-0039.2000.550205.x. PMID:10746785 doi:http://dx.doi.org/10.1034/j.1399-0039.2000.550205.x
6. ↑ Friese MA, Jakobsen KB, Friis L, Etzensperger R, Craner MJ, McMahon RM, Jensen LT, Huygelen V, Jones EY, Bell JI, Fugger L. Opposing effects of HLA class I molecules in tuning autoreactive CD8+ T cells in multiple sclerosis. Nat Med. 2008 Nov;14(11):1227-35. doi: 10.1038/nm.1881. Epub 2008 Oct 26. PMID:18953350 doi:http://dx.doi.org/10.1038/nm.1881
7. ↑ Nakamura J, Meguro A, Ishii G, Mihara T, Takeuchi M, Mizuki Y, Yuda K, Yamane T, Kawagoe T, Ota M, Mizuki N. The association analysis between HLA-A*26 and Behcet's disease. Sci Rep. 2019 Mar 14;9(1):4426. doi: 10.1038/s41598-019-40824-y. PMID:30872678 doi:http://dx.doi.org/10.1038/s41598-019-40824-y
8. ↑ LeHoang P, Ozdemir N, Benhamou A, Tabary T, Edelson C, Betuel H, Semiglia R, Cohen JH. HLA-A29.2 subtype associated with birdshot retinochoroidopathy. Am J Ophthalmol. 1992 Jan 15;113(1):33-5. doi: 10.1016/s0002-9394(14)75749-6. PMID:1728143 doi:http://dx.doi.org/10.1016/s0002-9394(14)75749-6
9. ↑ Fukada K, Chujoh Y, Tomiyama H, Miwa K, Kaneko Y, Oka S, Takiguchi M. HLA-A*1101-restricted cytotoxic T lymphocyte recognition of HIV-1 Pol protein. AIDS. 1999 Jul 30;13(11):1413-4. doi: 10.1097/00002030-199907300-00021. PMID:10449296 doi:http://dx.doi.org/10.1097/00002030-199907300-00021
10. ↑ Nagata Y, Ono S, Matsuo M, Gnjatic S, Valmori D, Ritter G, Garrett W, Old LJ, Mellman I. Differential presentation of a soluble exogenous tumor antigen, NY-ESO-1, by distinct human dendritic cell populations. Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10629-34. doi:, 10.1073/pnas.112331099. Epub 2002 Jul 23. PMID:12138174 doi:http://dx.doi.org/10.1073/pnas.112331099
11. ↑ Kuzushima K, Hayashi N, Kudoh A, Akatsuka Y, Tsujimura K, Morishima Y, Tsurumi T. Tetramer-assisted identification and characterization of epitopes recognized by HLA A*2402-restricted Epstein-Barr virus-specific CD8+ T cells. Blood. 2003 Feb 15;101(4):1460-8. doi: 10.1182/blood-2002-04-1240. Epub 2002 Sep , 26. PMID:12393434 doi:http://dx.doi.org/10.1182/blood-2002-04-1240
12. ↑ Stewart-Jones GB, McMichael AJ, Bell JI, Stuart DI, Jones EY. A structural basis for immunodominant human T cell receptor recognition. Nat Immunol. 2003 Jul;4(7):657-63. Epub 2003 Jun 8. PMID:12796775 doi:10.1038/ni942
13. ↑ Traversari C, van der Bruggen P, Luescher IF, Lurquin C, Chomez P, Van Pel A, De Plaen E, Amar-Costesec A, Boon T. A nonapeptide encoded by human gene MAGE-1 is recognized on HLA-A1 by cytolytic T lymphocytes directed against tumor antigen MZ2-E. J Exp Med. 1992 Nov 1;176(5):1453-7. doi: 10.1084/jem.176.5.1453. PMID:1402688 doi:http://dx.doi.org/10.1084/jem.176.5.1453
14. ↑ Satoh M, Takamiya Y, Oka S, Tokunaga K, Takiguchi M. Identification and characterization of HIV-1-specific CD8+ T cell epitopes presented by HLA-A*2601. Vaccine. 2005 May 31;23(29):3783-90. doi: 10.1016/j.vaccine.2005.02.022. Epub, 2005 Mar 17. PMID:15893615 doi:http://dx.doi.org/10.1016/j.vaccine.2005.02.022
15. ↑ Robek MD, Garcia ML, Boyd BS, Chisari FV. Role of immunoproteasome catalytic subunits in the immune response to hepatitis B virus. J Virol. 2007 Jan;81(2):483-91. doi: 10.1128/JVI.01779-06. Epub 2006 Nov 1. PMID:17079320 doi:http://dx.doi.org/10.1128/JVI.01779-06
16. ↑ Asemissen AM, Keilholz U, Tenzer S, Muller M, Walter S, Stevanovic S, Schild H, Letsch A, Thiel E, Rammensee HG, Scheibenbogen C. Identification of a highly immunogenic HLA-A*01-binding T cell epitope of WT1. Clin Cancer Res. 2006 Dec 15;12(24):7476-82. doi: 10.1158/1078-0432.CCR-06-1337. PMID:17189421 doi:http://dx.doi.org/10.1158/1078-0432.CCR-06-1337
17. ↑ Ishizuka J, Stewart-Jones GB, van der Merwe A, Bell JI, McMichael AJ, Jones EY. The structural dynamics and energetics of an immunodominant T cell receptor are programmed by its Vbeta domain. Immunity. 2008 Feb;28(2):171-82. PMID:18275829 doi:http://dx.doi.org/10.1016/j.immuni.2007.12.018
18. ↑ Gras S, Saulquin X, Reiser JB, Debeaupuis E, Echasserieau K, Kissenpfennig A, Legoux F, Chouquet A, Le Gorrec M, Machillot P, Neveu B, Thielens N, Malissen B, Bonneville M, Housset D. Structural bases for the affinity-driven selection of a public TCR against a dominant human cytomegalovirus epitope. J Immunol. 2009 Jul 1;183(1):430-7. PMID:19542454 doi:183/1/430
19. ↑ Hadrup SR, Bakker AH, Shu CJ, Andersen RS, van Veluw J, Hombrink P, Castermans E, Thor Straten P, Blank C, Haanen JB, Heemskerk MH, Schumacher TN. Parallel detection of antigen-specific T-cell responses by multidimensional encoding of MHC multimers. Nat Methods. 2009 Jul;6(7):520-6. doi: 10.1038/nmeth.1345. Epub 2009 Jun 21. PMID:19543285 doi:http://dx.doi.org/10.1038/nmeth.1345
20. ↑ Parmentier N, Stroobant V, Colau D, de Diesbach P, Morel S, Chapiro J, van Endert P, Van den Eynde BJ. Production of an antigenic peptide by insulin-degrading enzyme. Nat Immunol. 2010 May;11(5):449-54. doi: 10.1038/ni.1862. Epub 2010 Apr 4. PMID:20364150 doi:http://dx.doi.org/10.1038/ni.1862
21. ↑ Matthews PC, Adland E, Listgarten J, Leslie A, Mkhwanazi N, Carlson JM, Harndahl M, Stryhn A, Payne RP, Ogwu A, Huang KH, Frater J, Paioni P, Kloverpris H, Jooste P, Goedhals D, van Vuuren C, Steyn D, Riddell L, Chen F, Luzzi G, Balachandran T, Ndung'u T, Buus S, Carrington M, Shapiro R, Heckerman D, Goulder PJ. HLA-A*7401-mediated control of HIV viremia is independent of its linkage disequilibrium with HLA-B*5703. J Immunol. 2011 May 15;186(10):5675-86. doi: 10.4049/jimmunol.1003711. Epub 2011 , Apr 15. PMID:21498667 doi:http://dx.doi.org/10.4049/jimmunol.1003711
22. ↑ Shimizu A, Kawana-Tachikawa A, Yamagata A, Han C, Zhu D, Sato Y, Nakamura H, Koibuchi T, Carlson J, Martin E, Brumme CJ, Shi Y, Gao GF, Brumme ZL, Fukai S, Iwamoto A. Structure of TCR and antigen complexes at an immunodominant CTL epitope in HIV-1 infection. Sci Rep. 2013 Nov 6;3:3097. doi: 10.1038/srep03097. PMID:24192765 doi:http://dx.doi.org/10.1038/srep03097
23. ↑ Quinones-Parra S, Grant E, Loh L, Nguyen TH, Campbell KA, Tong SY, Miller A, Doherty PC, Vijaykrishna D, Rossjohn J, Gras S, Kedzierska K. Preexisting CD8+ T-cell immunity to the H7N9 influenza A virus varies across ethnicities. Proc Natl Acad Sci U S A. 2014 Jan 21;111(3):1049-54. doi:, 10.1073/pnas.1322229111. Epub 2014 Jan 6. PMID:24395804 doi:http://dx.doi.org/10.1073/pnas.1322229111
24. ↑ Jelachich ML, Cowan EP, Turner RV, Coligan JE, Biddison WE. Analysis of the molecular basis of HLA-A3 recognition by cytotoxic T cells using defined mutants of the HLA-A3 molecule. J Immunol. 1988 Aug 15;141(4):1108-13. PMID:2456340
25. ↑ Giam K, Ayala-Perez R, Illing PT, Schittenhelm RB, Croft NP, Purcell AW, Dudek NL. A comprehensive analysis of peptides presented by HLA-A1. Tissue Antigens. 2015 Jun;85(6):492-6. doi: 10.1111/tan.12565. Epub 2015 Apr 16. PMID:25880248 doi:http://dx.doi.org/10.1111/tan.12565
26. ↑ Tripathi SC, Peters HL, Taguchi A, Katayama H, Wang H, Momin A, Jolly MK, Celiktas M, Rodriguez-Canales J, Liu H, Behrens C, Wistuba II, Ben-Jacob E, Levine H, Molldrem JJ, Hanash SM, Ostrin EJ. Immunoproteasome deficiency is a feature of non-small cell lung cancer with a mesenchymal phenotype and is associated with a poor outcome. Proc Natl Acad Sci U S A. 2016 Mar 15;113(11):E1555-64. doi:, 10.1073/pnas.1521812113. Epub 2016 Feb 29. PMID:26929325 doi:http://dx.doi.org/10.1073/pnas.1521812113
27. ↑ Ebstein F, Textoris-Taube K, Keller C, Golnik R, Vigneron N, Van den Eynde BJ, Schuler-Thurner B, Schadendorf D, Lorenz FK, Uckert W, Urban S, Lehmann A, Albrecht-Koepke N, Janek K, Henklein P, Niewienda A, Kloetzel PM, Mishto M. Proteasomes generate spliced epitopes by two different mechanisms and as efficiently as non-spliced epitopes. Sci Rep. 2016 Apr 6;6:24032. doi: 10.1038/srep24032. PMID:27049119 doi:http://dx.doi.org/10.1038/srep24032
28. ↑ Salter RD, Norment AM, Chen BP, Clayberger C, Krensky AM, Littman DR, Parham P. Polymorphism in the alpha 3 domain of HLA-A molecules affects binding to CD8. Nature. 1989 Mar 23;338(6213):345-7. doi: 10.1038/338345a0. PMID:2784196 doi:http://dx.doi.org/10.1038/338345a0
29. ↑ Song I, Gil A, Mishra R, Ghersi D, Selin LK, Stern LJ. Broad TCR repertoire and diverse structural solutions for recognition of an immunodominant CD8+ T cell epitope. Nat Struct Mol Biol. 2017 Feb 27. doi: 10.1038/nsmb.3383. PMID:28250417 doi:http://dx.doi.org/10.1038/nsmb.3383
30. ↑ DiBrino M, Tsuchida T, Turner RV, Parker KC, Coligan JE, Biddison WE. HLA-A1 and HLA-A3 T cell epitopes derived from influenza virus proteins predicted from peptide binding motifs. J Immunol. 1993 Dec 1;151(11):5930-5. PMID:7504010
31. ↑ DiBrino M, Parker KC, Shiloach J, Turner RV, Tsuchida T, Garfield M, Biddison WE, Coligan JE. Endogenous peptides with distinct amino acid anchor residue motifs bind to HLA-A1 and HLA-B8. J Immunol. 1994 Jan 15;152(2):620-31. PMID:7506728
32. ↑ DiBrino M, Parker KC, Shiloach J, Knierman M, Lukszo J, Turner RV, Biddison WE, Coligan JE. Endogenous peptides bound to HLA-A3 possess a specific combination of anchor residues that permit identification of potential antigenic peptides. Proc Natl Acad Sci U S A. 1993 Feb 15;90(4):1508-12. doi: 10.1073/pnas.90.4.1508. PMID:7679507 doi:http://dx.doi.org/10.1073/pnas.90.4.1508
33. ↑ Madden DR, Garboczi DN, Wiley DC. The antigenic identity of peptide-MHC complexes: a comparison of the conformations of five viral peptides presented by HLA-A2. Cell. 1993 Nov 19;75(4):693-708. PMID:7694806
34. ↑ Kawakami Y, Robbins PF, Wang X, Tupesis JP, Parkhurst MR, Kang X, Sakaguchi K, Appella E, Rosenberg SA. Identification of new melanoma epitopes on melanosomal proteins recognized by tumor infiltrating T lymphocytes restricted by HLA-A1, -A2, and -A3 alleles. J Immunol. 1998 Dec 15;161(12):6985-92. PMID:9862734
35. ↑ Traversari C, van der Bruggen P, Luescher IF, Lurquin C, Chomez P, Van Pel A, De Plaen E, Amar-Costesec A, Boon T. A nonapeptide encoded by human gene MAGE-1 is recognized on HLA-A1 by cytolytic T lymphocytes directed against tumor antigen MZ2-E. J Exp Med. 1992 Nov 1;176(5):1453-7. doi: 10.1084/jem.176.5.1453. PMID:1402688 doi:http://dx.doi.org/10.1084/jem.176.5.1453
36. ↑ Asemissen AM, Keilholz U, Tenzer S, Muller M, Walter S, Stevanovic S, Schild H, Letsch A, Thiel E, Rammensee HG, Scheibenbogen C. Identification of a highly immunogenic HLA-A*01-binding T cell epitope of WT1. Clin Cancer Res. 2006 Dec 15;12(24):7476-82. doi: 10.1158/1078-0432.CCR-06-1337. PMID:17189421 doi:http://dx.doi.org/10.1158/1078-0432.CCR-06-1337
37. ↑ Brennan RM, Burrows SR. A mechanism for the HLA-A*01-associated risk for EBV+ Hodgkin lymphoma and infectious mononucleosis. Blood. 2008 Sep 15;112(6):2589-90. doi: 10.1182/blood-2008-06-162883. PMID:18779413 doi:http://dx.doi.org/10.1182/blood-2008-06-162883
38. ↑ Kumar P, Vahedi-Faridi A, Saenger W, Ziegler A, Uchanska-Ziegler B. Conformational changes within the HLA-A1:MAGE-A1 complex induced by binding of a recombinant antibody fragment with TCR-like specificity. Protein Sci. 2009 Jan;18(1):37-49. PMID:19177349 doi:10.1002/pro.4
39. ↑ Parmentier N, Stroobant V, Colau D, de Diesbach P, Morel S, Chapiro J, van Endert P, Van den Eynde BJ. Production of an antigenic peptide by insulin-degrading enzyme. Nat Immunol. 2010 May;11(5):449-54. doi: 10.1038/ni.1862. Epub 2010 Apr 4. PMID:20364150 doi:http://dx.doi.org/10.1038/ni.1862
40. ↑ Quinones-Parra S, Grant E, Loh L, Nguyen TH, Campbell KA, Tong SY, Miller A, Doherty PC, Vijaykrishna D, Rossjohn J, Gras S, Kedzierska K. Preexisting CD8+ T-cell immunity to the H7N9 influenza A virus varies across ethnicities. Proc Natl Acad Sci U S A. 2014 Jan 21;111(3):1049-54. doi:, 10.1073/pnas.1322229111. Epub 2014 Jan 6. PMID:24395804 doi:http://dx.doi.org/10.1073/pnas.1322229111
41. ↑ Giam K, Ayala-Perez R, Illing PT, Schittenhelm RB, Croft NP, Purcell AW, Dudek NL. A comprehensive analysis of peptides presented by HLA-A1. Tissue Antigens. 2015 Jun;85(6):492-6. doi: 10.1111/tan.12565. Epub 2015 Apr 16. PMID:25880248 doi:http://dx.doi.org/10.1111/tan.12565
42. ↑ Raman MC, Rizkallah PJ, Simmons R, Donnellan Z, Dukes J, Bossi G, Le Provost GS, Todorov P, Baston E, Hickman E, Mahon T, Hassan N, Vuidepot A, Sami M, Cole DK, Jakobsen BK. Direct molecular mimicry enables off-target cardiovascular toxicity by an enhanced affinity TCR designed for cancer immunotherapy. Sci Rep. 2016 Jan 13;6:18851. doi: 10.1038/srep18851. PMID:26758806 doi:http://dx.doi.org/10.1038/srep18851
43. ↑ Keib A, Mei YF, Cicin-Sain L, Busch DH, Dennehy KM. Measuring Antiviral Capacity of T Cell Responses to Adenovirus. J Immunol. 2019 Jan 15;202(2):618-624. doi: 10.4049/jimmunol.1801003. Epub 2018, Dec 7. PMID:30530481 doi:http://dx.doi.org/10.4049/jimmunol.1801003
44. ↑ DiBrino M, Tsuchida T, Turner RV, Parker KC, Coligan JE, Biddison WE. HLA-A1 and HLA-A3 T cell epitopes derived from influenza virus proteins predicted from peptide binding motifs. J Immunol. 1993 Dec 1;151(11):5930-5. PMID:7504010
45. ↑ Hillig RC, Coulie PG, Stroobant V, Saenger W, Ziegler A, Hulsmeyer M. High-resolution structure of HLA-A*0201 in complex with a tumour-specific antigenic peptide encoded by the MAGE-A4 gene. J Mol Biol. 2001 Jul 27;310(5):1167-76. PMID:11502003 doi:10.1006/jmbi.2001.4816
46. ↑ Nagata Y, Ono S, Matsuo M, Gnjatic S, Valmori D, Ritter G, Garrett W, Old LJ, Mellman I. Differential presentation of a soluble exogenous tumor antigen, NY-ESO-1, by distinct human dendritic cell populations. Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10629-34. doi:, 10.1073/pnas.112331099. Epub 2002 Jul 23. PMID:12138174 doi:http://dx.doi.org/10.1073/pnas.112331099
47. ↑ Stewart-Jones GB, McMichael AJ, Bell JI, Stuart DI, Jones EY. A structural basis for immunodominant human T cell receptor recognition. Nat Immunol. 2003 Jul;4(7):657-63. Epub 2003 Jun 8. PMID:12796775 doi:10.1038/ni942
48. ↑ Robek MD, Garcia ML, Boyd BS, Chisari FV. Role of immunoproteasome catalytic subunits in the immune response to hepatitis B virus. J Virol. 2007 Jan;81(2):483-91. doi: 10.1128/JVI.01779-06. Epub 2006 Nov 1. PMID:17079320 doi:http://dx.doi.org/10.1128/JVI.01779-06
49. ↑ Ishizuka J, Stewart-Jones GB, van der Merwe A, Bell JI, McMichael AJ, Jones EY. The structural dynamics and energetics of an immunodominant T cell receptor are programmed by its Vbeta domain. Immunity. 2008 Feb;28(2):171-82. PMID:18275829 doi:http://dx.doi.org/10.1016/j.immuni.2007.12.018
50. ↑ Gras S, Saulquin X, Reiser JB, Debeaupuis E, Echasserieau K, Kissenpfennig A, Legoux F, Chouquet A, Le Gorrec M, Machillot P, Neveu B, Thielens N, Malissen B, Bonneville M, Housset D. Structural bases for the affinity-driven selection of a public TCR against a dominant human cytomegalovirus epitope. J Immunol. 2009 Jul 1;183(1):430-7. PMID:19542454 doi:183/1/430
51. ↑ Borbulevych OY, Do P, Baker BM. Structures of native and affinity-enhanced WT1 epitopes bound to HLA-A*0201: implications for WT1-based cancer therapeutics. Mol Immunol. 2010 Sep;47(15):2519-24. Epub 2010 Jul 8. PMID:20619457 doi:10.1016/j.molimm.2010.06.005
52. ↑ Bulek AM, Cole DK, Skowera A, Dolton G, Gras S, Madura F, Fuller A, Miles JJ, Gostick E, Price DA, Drijfhout JW, Knight RR, Huang GC, Lissin N, Molloy PE, Wooldridge L, Jakobsen BK, Rossjohn J, Peakman M, Rizkallah PJ, Sewell AK. Structural basis for the killing of human beta cells by CD8(+) T cells in type 1 diabetes. Nat Immunol. 2012 Jan 15. doi: 10.1038/ni.2206. PMID:22245737 doi:10.1038/ni.2206
53. ↑ Tripathi SC, Peters HL, Taguchi A, Katayama H, Wang H, Momin A, Jolly MK, Celiktas M, Rodriguez-Canales J, Liu H, Behrens C, Wistuba II, Ben-Jacob E, Levine H, Molldrem JJ, Hanash SM, Ostrin EJ. Immunoproteasome deficiency is a feature of non-small cell lung cancer with a mesenchymal phenotype and is associated with a poor outcome. Proc Natl Acad Sci U S A. 2016 Mar 15;113(11):E1555-64. doi:, 10.1073/pnas.1521812113. Epub 2016 Feb 29. PMID:26929325 doi:http://dx.doi.org/10.1073/pnas.1521812113
54. ↑ Salter RD, Norment AM, Chen BP, Clayberger C, Krensky AM, Littman DR, Parham P. Polymorphism in the alpha 3 domain of HLA-A molecules affects binding to CD8. Nature. 1989 Mar 23;338(6213):345-7. doi: 10.1038/338345a0. PMID:2784196 doi:http://dx.doi.org/10.1038/338345a0
55. ↑ Song I, Gil A, Mishra R, Ghersi D, Selin LK, Stern LJ. Broad TCR repertoire and diverse structural solutions for recognition of an immunodominant CD8+ T cell epitope. Nat Struct Mol Biol. 2017 Feb 27. doi: 10.1038/nsmb.3383. PMID:28250417 doi:http://dx.doi.org/10.1038/nsmb.3383
56. ↑ Madden DR, Garboczi DN, Wiley DC. The antigenic identity of peptide-MHC complexes: a comparison of the conformations of five viral peptides presented by HLA-A2. Cell. 1993 Nov 19;75(4):693-708. PMID:7694806
57. ↑ Collins EJ, Garboczi DN, Wiley DC. Three-dimensional structure of a peptide extending from one end of a class I MHC binding site. Nature. 1994 Oct 13;371(6498):626-9. PMID:7935798 doi:http://dx.doi.org/10.1038/371626a0
58. ↑ Peace-Brewer AL, Tussey LG, Matsui M, Li G, Quinn DG, Frelinger JA. A point mutation in HLA-A*0201 results in failure to bind the TAP complex and to present virus-derived peptides to CTL. Immunity. 1996 May;4(5):505-14. doi: 10.1016/s1074-7613(00)80416-1. PMID:8630735 doi:http://dx.doi.org/10.1016/s1074-7613(00)80416-1
59. ↑ Lewis JW, Neisig A, Neefjes J, Elliott T. Point mutations in the alpha 2 domain of HLA-A2.1 define a functionally relevant interaction with TAP. Curr Biol. 1996 Jul 1;6(7):873-83. doi: 10.1016/s0960-9822(02)00611-5. PMID:8805302 doi:http://dx.doi.org/10.1016/s0960-9822(02)00611-5
60. ↑ Garboczi DN, Ghosh P, Utz U, Fan QR, Biddison WE, Wiley DC. Structure of the complex between human T-cell receptor, viral peptide and HLA-A2. Nature. 1996 Nov 14;384(6605):134-41. PMID:8906788 doi:10.1038/384134a0
61. ↑ Gao GF, Tormo J, Gerth UC, Wyer JR, McMichael AJ, Stuart DI, Bell JI, Jones EY, Jakobsen BK. Crystal structure of the complex between human CD8alpha(alpha) and HLA-A2. Nature. 1997 Jun 5;387(6633):630-4. PMID:9177355 doi:http://dx.doi.org/10.1038/42523
62. ↑ Hadrup SR, Bakker AH, Shu CJ, Andersen RS, van Veluw J, Hombrink P, Castermans E, Thor Straten P, Blank C, Haanen JB, Heemskerk MH, Schumacher TN. Parallel detection of antigen-specific T-cell responses by multidimensional encoding of MHC multimers. Nat Methods. 2009 Jul;6(7):520-6. doi: 10.1038/nmeth.1345. Epub 2009 Jun 21. PMID:19543285 doi:http://dx.doi.org/10.1038/nmeth.1345
63. ↑ Zhang S, Liu J, Cheng H, Tan S, Qi J, Yan J, Gao GF. Structural basis of cross-allele presentation by HLA-A*0301 and HLA-A*1101 revealed by two HIV-derived peptide complexes. Mol Immunol. 2011 Oct;49(1-2):395-401. Epub 2011 Sep 25. PMID:21943705 doi:10.1016/j.molimm.2011.08.015
64. ↑ Jelachich ML, Cowan EP, Turner RV, Coligan JE, Biddison WE. Analysis of the molecular basis of HLA-A3 recognition by cytotoxic T cells using defined mutants of the HLA-A3 molecule. J Immunol. 1988 Aug 15;141(4):1108-13. PMID:2456340
65. ↑ Ebstein F, Textoris-Taube K, Keller C, Golnik R, Vigneron N, Van den Eynde BJ, Schuler-Thurner B, Schadendorf D, Lorenz FK, Uckert W, Urban S, Lehmann A, Albrecht-Koepke N, Janek K, Henklein P, Niewienda A, Kloetzel PM, Mishto M. Proteasomes generate spliced epitopes by two different mechanisms and as efficiently as non-spliced epitopes. Sci Rep. 2016 Apr 6;6:24032. doi: 10.1038/srep24032. PMID:27049119 doi:http://dx.doi.org/10.1038/srep24032
66. ↑ DiBrino M, Tsuchida T, Turner RV, Parker KC, Coligan JE, Biddison WE. HLA-A1 and HLA-A3 T cell epitopes derived from influenza virus proteins predicted from peptide binding motifs. J Immunol. 1993 Dec 1;151(11):5930-5. PMID:7504010
67. ↑ DiBrino M, Parker KC, Shiloach J, Knierman M, Lukszo J, Turner RV, Biddison WE, Coligan JE. Endogenous peptides bound to HLA-A3 possess a specific combination of anchor residues that permit identification of potential antigenic peptides. Proc Natl Acad Sci U S A. 1993 Feb 15;90(4):1508-12. doi: 10.1073/pnas.90.4.1508. PMID:7679507 doi:http://dx.doi.org/10.1073/pnas.90.4.1508
68. ↑ Kawakami Y, Robbins PF, Wang X, Tupesis JP, Parkhurst MR, Kang X, Sakaguchi K, Appella E, Rosenberg SA. Identification of new melanoma epitopes on melanosomal proteins recognized by tumor infiltrating T lymphocytes restricted by HLA-A1, -A2, and -A3 alleles. J Immunol. 1998 Dec 15;161(12):6985-92. PMID:9862734
69. ↑ Fukada K, Chujoh Y, Tomiyama H, Miwa K, Kaneko Y, Oka S, Takiguchi M. HLA-A*1101-restricted cytotoxic T lymphocyte recognition of HIV-1 Pol protein. AIDS. 1999 Jul 30;13(11):1413-4. doi: 10.1097/00002030-199907300-00021. PMID:10449296 doi:http://dx.doi.org/10.1097/00002030-199907300-00021
70. ↑ Peng Y, Mentzer AJ, Liu G, Yao X, Yin Z, Dong D, Dejnirattisai W, Rostron T, Supasa P, Liu C, Lopez-Camacho C, Slon-Campos J, Zhao Y, Stuart DI, Paesen GC, Grimes JM, Antson AA, Bayfield OW, Hawkins DEDP, Ker DS, Wang B, Turtle L, Subramaniam K, Thomson P, Zhang P, Dold C, Ratcliff J, Simmonds P, de Silva T, Sopp P, Wellington D, Rajapaksa U, Chen YL, Salio M, Napolitani G, Paes W, Borrow P, Kessler BM, Fry JW, Schwabe NF, Semple MG, Baillie JK, Moore SC, Openshaw PJM, Ansari MA, Dunachie S, Barnes E, Frater J, Kerr G, Goulder P, Lockett T, Levin R, Zhang Y, Jing R, Ho LP, Cornall RJ, Conlon CP, Klenerman P, Screaton GR, Mongkolsapaya J, McMichael A, Knight JC, Ogg G, Dong T. Broad and strong memory CD4(+) and CD8(+) T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19. Nat Immunol. 2020 Nov;21(11):1336-1345. doi: 10.1038/s41590-020-0782-6. Epub 2020, Sep 4. PMID:32887977 doi:http://dx.doi.org/10.1038/s41590-020-0782-6
71. ↑ Thananchai H, Gillespie G, Martin MP, Bashirova A, Yawata N, Yawata M, Easterbrook P, McVicar DW, Maenaka K, Parham P, Carrington M, Dong T, Rowland-Jones S. Cutting Edge: Allele-specific and peptide-dependent interactions between KIR3DL1 and HLA-A and HLA-B. J Immunol. 2007 Jan 1;178(1):33-7. doi: 10.4049/jimmunol.178.1.33. PMID:17182537 doi:http://dx.doi.org/10.4049/jimmunol.178.1.33
72. ↑ Kuzushima K, Hayashi N, Kudoh A, Akatsuka Y, Tsujimura K, Morishima Y, Tsurumi T. Tetramer-assisted identification and characterization of epitopes recognized by HLA A*2402-restricted Epstein-Barr virus-specific CD8+ T cells. Blood. 2003 Feb 15;101(4):1460-8. doi: 10.1182/blood-2002-04-1240. Epub 2002 Sep , 26. PMID:12393434 doi:http://dx.doi.org/10.1182/blood-2002-04-1240
73. ↑ Thananchai H, Gillespie G, Martin MP, Bashirova A, Yawata N, Yawata M, Easterbrook P, McVicar DW, Maenaka K, Parham P, Carrington M, Dong T, Rowland-Jones S. Cutting Edge: Allele-specific and peptide-dependent interactions between KIR3DL1 and HLA-A and HLA-B. J Immunol. 2007 Jan 1;178(1):33-7. doi: 10.4049/jimmunol.178.1.33. PMID:17182537 doi:http://dx.doi.org/10.4049/jimmunol.178.1.33
74. ↑ Stern M, Ruggeri L, Capanni M, Mancusi A, Velardi A. Human leukocyte antigens A23, A24, and A32 but not A25 are ligands for KIR3DL1. Blood. 2008 Aug 1;112(3):708-10. doi: 10.1182/blood-2008-02-137521. Epub 2008 May, 23. PMID:18502829 doi:http://dx.doi.org/10.1182/blood-2008-02-137521
75. ↑ Liu J, Wu P, Gao F, Qi J, Kawana-Tachikawa A, Xie J, Vavricka CJ, Iwamoto A, Li T, Gao GF. Novel immunodominant peptide presentation strategy: a featured HLA-A*2402-restricted cytotoxic T-lymphocyte epitope stabilized by intrachain hydrogen bonds from severe acute respiratory syndrome coronavirus nucleocapsid protein. J Virol. 2010 Nov;84(22):11849-57. Epub 2010 Sep 15. PMID:20844028 doi:10.1128/JVI.01464-10
76. ↑ Shimizu A, Kawana-Tachikawa A, Yamagata A, Han C, Zhu D, Sato Y, Nakamura H, Koibuchi T, Carlson J, Martin E, Brumme CJ, Shi Y, Gao GF, Brumme ZL, Fukai S, Iwamoto A. Structure of TCR and antigen complexes at an immunodominant CTL epitope in HIV-1 infection. Sci Rep. 2013 Nov 6;3:3097. doi: 10.1038/srep03097. PMID:24192765 doi:http://dx.doi.org/10.1038/srep03097
77. ↑ Ikeda H, Lethe B, Lehmann F, van Baren N, Baurain JF, de Smet C, Chambost H, Vitale M, Moretta A, Boon T, Coulie PG. Characterization of an antigen that is recognized on a melanoma showing partial HLA loss by CTL expressing an NK inhibitory receptor. Immunity. 1997 Feb;6(2):199-208. PMID:9047241
78. ↑ Satoh M, Takamiya Y, Oka S, Tokunaga K, Takiguchi M. Identification and characterization of HIV-1-specific CD8+ T cell epitopes presented by HLA-A*2601. Vaccine. 2005 May 31;23(29):3783-90. doi: 10.1016/j.vaccine.2005.02.022. Epub, 2005 Mar 17. PMID:15893615 doi:http://dx.doi.org/10.1016/j.vaccine.2005.02.022
79. ↑ Boisgerault F, Khalil I, Tieng V, Connan F, Tabary T, Cohen JH, Choppin J, Charron D, Toubert A. Definition of the HLA-A29 peptide ligand motif allows prediction of potential T-cell epitopes from the retinal soluble antigen, a candidate autoantigen in birdshot retinopathy. Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3466-70. doi: 10.1073/pnas.93.8.3466. PMID:8622959 doi:http://dx.doi.org/10.1073/pnas.93.8.3466
80. ↑ Thananchai H, Gillespie G, Martin MP, Bashirova A, Yawata N, Yawata M, Easterbrook P, McVicar DW, Maenaka K, Parham P, Carrington M, Dong T, Rowland-Jones S. Cutting Edge: Allele-specific and peptide-dependent interactions between KIR3DL1 and HLA-A and HLA-B. J Immunol. 2007 Jan 1;178(1):33-7. doi: 10.4049/jimmunol.178.1.33. PMID:17182537 doi:http://dx.doi.org/10.4049/jimmunol.178.1.33
81. ↑ Guo HC, Jardetzky TS, Garrett TP, Lane WS, Strominger JL, Wiley DC. Different length peptides bind to HLA-Aw68 similarly at their ends but bulge out in the middle. Nature. 1992 Nov 26;360(6402):364-6. PMID:1448153 doi:http://dx.doi.org/10.1038/360364a0
82. ↑ Silver ML, Guo HC, Strominger JL, Wiley DC. Atomic structure of a human MHC molecule presenting an influenza virus peptide. Nature. 1992 Nov 26;360(6402):367-9. doi: 10.1038/360367a0. PMID:1448154 doi:http://dx.doi.org/10.1038/360367a0
83. ↑ Salter RD, Norment AM, Chen BP, Clayberger C, Krensky AM, Littman DR, Parham P. Polymorphism in the alpha 3 domain of HLA-A molecules affects binding to CD8. Nature. 1989 Mar 23;338(6213):345-7. doi: 10.1038/338345a0. PMID:2784196 doi:http://dx.doi.org/10.1038/338345a0
84. ↑ Matthews PC, Adland E, Listgarten J, Leslie A, Mkhwanazi N, Carlson JM, Harndahl M, Stryhn A, Payne RP, Ogwu A, Huang KH, Frater J, Paioni P, Kloverpris H, Jooste P, Goedhals D, van Vuuren C, Steyn D, Riddell L, Chen F, Luzzi G, Balachandran T, Ndung'u T, Buus S, Carrington M, Shapiro R, Heckerman D, Goulder PJ. HLA-A*7401-mediated control of HIV viremia is independent of its linkage disequilibrium with HLA-B*5703. J Immunol. 2011 May 15;186(10):5675-86. doi: 10.4049/jimmunol.1003711. Epub 2011 , Apr 15. PMID:21498667 doi:http://dx.doi.org/10.4049/jimmunol.1003711
85. ↑ Remesh SG, Andreatta M, Ying G, Kaever T, Nielsen M, McMurtrey C, Hildebrand W, Peters B, Zajonc DM. Unconventional Peptide Presentation by Major Histocompatibility Complex (MHC) Class I Allele HLA-A*02:01: BREAKING CONFINEMENT. J Biol Chem. 2017 Mar 31;292(13):5262-5270. doi: 10.1074/jbc.M117.776542. Epub, 2017 Feb 8. PMID:28179428 doi:http://dx.doi.org/10.1074/jbc.M117.776542