1932

Abstract

Possession of the human leukocyte antigen (HLA) class I molecule B27 is strongly associated with ankylosing spondylitis (AS), but the pathogenic role of HLA-B27 is unknown. Two broad theories most likely explain the role of HLA-B27 in AS pathogenesis. The first is based on the natural immunological function of HLA-B27 of presenting antigenic peptides to cytotoxic T cells. Thus, HLA-B27-restricted immune responses to self-antigens, or arthritogenic peptides, might drive immunopathology. B27 can also “behave badly,” misfolding during assembly and leading to endoplasmic reticulum stress and autophagy responses. βm-free B27 heavy chain structures including homodimers (B27) can also be expressed at the cell surface following endosomal recycling of cell surface heterotrimers. Cell surface free heavy chains and B27 bind to innate immune receptors on T, NK, and myeloid cells with proinflammatory effects. This review describes the natural function of HLA-B27, its disease associations, and the current theories as to its pathogenic role.

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2015-03-21
2024-04-20
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Literature Cited

  1. Zinkernagel RM, Doherty PC. 1.  1973. Cytotoxic thymus-derived lymphocytes in cerebrospinal fluid of mice with lymphocytic choriomeningitis. J. Exp. Med. 138:51266–69 [Google Scholar]
  2. Zinkernagel RM, Doherty PC. 2.  1974. Restriction of in vitro T cell–mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system. Nature 248:5450701–2 [Google Scholar]
  3. Townsend AR, Rothbard J, Gotch FM, Bahadur G, Wraith D, McMichael AJ. 3.  1986. The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell 44:6959–68 [Google Scholar]
  4. Nixon DF, Townsend AR, Elvin JG, Rizza CR, Gallwey J, McMichael AJ. 4.  1988. HIV-1 gag-specific cytotoxic T lymphocytes defined with recombinant vaccinia virus and synthetic peptides. Nature 336:6198484–87 [Google Scholar]
  5. Huet S, Nixon DF, Rothbard JB, Townsend A, Ellis SA, McMichael AJ. 5.  1990. Structural homologies between two HLA B27–restricted peptides suggest residues important for interaction with HLA B27. Int. Immunol. 2:4311–16 [Google Scholar]
  6. Madden DR, Gorga JC, Strominger JL, Wiley DC. 6.  1991. The structure of HLA-B27 reveals nonamer self-peptides bound in an extended conformation. Nature 353:6342321–25 [Google Scholar]
  7. Madden DR, Gorga JC, Strominger JL, Wiley DC. 7.  1992. The three-dimensional structure of HLA-B27 at 2.1 Å resolution suggests a general mechanism for tight peptide binding to MHC. Cell 70:61035–48 [Google Scholar]
  8. Jardetzky TS, Lane WS, Robinson RA, Madden DR, Wiley DC. 8.  1991. Identification of self peptides bound to purified HLA-B27. Nature 353:6342326–29 [Google Scholar]
  9. Brooks JM, Murray RJ, Thomas WA, Kurilla MG, Rickinson AB. 9.  1993. Different HLA-B27 subtypes present the same immunodominant Epstein-Barr virus peptide. J. Exp. Med. 178:3879–87 [Google Scholar]
  10. Raghavan M, Lebrón JA, Johnson JL, Bjorkman PJ. 10.  1996. Extended repertoire of permissible peptide ligands for HLA-B*2702. Protein Sci. 5:102080–88 [Google Scholar]
  11. Blum JS, Wearsch PA, Cresswell P. 11.  2013. Pathways of antigen processing. Annu. Rev. Immunol. 31:443–73 [Google Scholar]
  12. Peh CA, Burrows SR, Barnden M, Khanna R, Cresswell P. 12.  et al. 1998. HLA-B27-restricted antigen presentation in the absence of tapasin reveals polymorphism in mechanisms of HLA class I peptide loading. Immunity 8:5531–42 [Google Scholar]
  13. Goulder PJ, Phillips RE, Colbert RA, McAdam S, Ogg G. 13.  et al. 1997. Late escape from an immunodominant cytotoxic T-lymphocyte response associated with progression to AIDS. Nat. Med. 3:2212–17 [Google Scholar]
  14. den Uyl D, van der Horst-Bruinsma IE, van Agtmael M. 14.  2004. Progression of HIV to AIDS: a protective role for HLA-B27?. AIDS Rev. 6:289–96 [Google Scholar]
  15. Dazert E, Neumann-Haefelin C, Bressanelli S, Fitzmaurice K, Kort J. 15.  et al. 2009. Loss of viral fitness and cross-recognition by CD8+ T cells limit HCV escape from a protective HLA-B27-restricted human immune response. J. Clin. Investig. 119:2376–86 [Google Scholar]
  16. Bowness P. 16.  2002. HLA B27 in health and disease: a double-edged sword?. Rheumatology 41:8857–68 [Google Scholar]
  17. Peruzzi M, Wagtmann N, Long EO. 17.  1996. A p70 killer cell inhibitory receptor specific for several HLA-B allotypes discriminates among peptides bound to HLA-B*2705. J. Exp. Med. 184:41585–90 [Google Scholar]
  18. Malnati MS, Peruzzi M, Parker KC, Biddison WE, Ciccone E. 18.  et al. 1995. Peptide specificity in the recognition of MHC class I by natural killer cell clones. Science 267:52001016–18 [Google Scholar]
  19. Stewart-Jones GBE, di Gleria K, Kollnberger S, McMichael AJ, Jones EY, Bowness P. 19.  2005. Crystal structures and KIR3DL1 recognition of three immunodominant viral peptides complexed to HLA-B*2705. Eur. J. Immunol. 35:2341–51 [Google Scholar]
  20. Colonna M, Samaridis J, Cella M, Angman L, Allen RL. 20.  et al. 1998. Cutting edge: Human myelomonocytic cells express an inhibitory receptor for classical and nonclassical MHC class I molecules. J. Immunol. 160:73096–100 [Google Scholar]
  21. Bashirova AA, Martin-Gayo E, Jones DC, Qi Y, Apps R. 21.  et al. 2014. LILRB2 interaction with HLA class I correlates with control of HIV-1 infection. PLOS Genet. 10:3e1004196 [Google Scholar]
  22. Urban RG, Chicz RM, Lane WS, Strominger JL, Rehm A. 22.  et al. 1994. A subset of HLA-B27 molecules contains peptides much longer than nonamers. PNAS 91:41534–38 [Google Scholar]
  23. Malik P, Klimovitsky P, Deng L-W, Boyson JE, Strominger JL. 23.  2002. Uniquely conformed peptide-containing β2-microglobulin-free heavy chains of HLA-B2705 on the cell surface. J. Immunol. Baltim. Md 1950 169:84379–87 [Google Scholar]
  24. Boyle LH, Goodall JC, Opat SS, Gaston JS. 24.  2001. The recognition of HLA-B27 by human CD4+ T lymphocytes. J. Immunol. 1950 167:52619–24 [Google Scholar]
  25. Roddis M, Carter RW, Sun M-Y, Weissensteiner T, McMichael AJ. 25.  et al. 2004. Fully functional HLA B27-restricted CD4+ as well as CD8+ T cell responses in TCR transgenic mice. J. Immunol. 1950 172:1155–61 [Google Scholar]
  26. Illing PT, Vivian JP, Dudek NL, Kostenko L, Chen Z. 26.  et al. 2012. Immune self-reactivity triggered by drug-modified HLA-peptide repertoire. Nature 486:7404554–58 [Google Scholar]
  27. Schnabl E, Stockinger H, Majdic O, Gaugitsch H, Lindley IJ. 27.  et al. 1990. Activated human T lymphocytes express MHC class I heavy chains not associated with β2-microglobulin. J. Exp. Med. 171:51431–42 [Google Scholar]
  28. Pickl WF, Majdic O, Faé I, Reuschel R, Holter W, Knapp W. 28.  1993. The soluble pool of beta 2–microglobulin free HLA class I alpha-chains: qualitative and quantitative characterization. J. Immunol. 151:52613–22 [Google Scholar]
  29. Lee H, Brott BK, Kirkby LA, Adelson JD, Cheng S. 29.  et al. 2014. Synapse elimination and learning rules co-regulated by MHC class I H2-Db. Nature 509:7499195–200 [Google Scholar]
  30. Winternitz JC, Minchey SG, Garamszegi LZ, Huang S, Stephens PR, Altizer S. 30.  2013. Sexual selection explains more functional variation in the mammalian major histocompatibility complex than parasitism. Proc. R. Soc. B 280:176920131605 [Google Scholar]
  31. Costantino F, Talpin A, Said-Nahal R, Goldberg M, Henny J. 31.  et al. 2013. Prevalence of spondyloarthritis in reference to HLA-B27 in the French population: results of the GAZEL cohort. Ann. Rheum. Dis. In press. doi: 10.1136/annrheumdis-2013-204436
  32. Reveille JD. 32.  2011. Epidemiology of spondyloarthritis in North America. Am. J. Med. Sci. 341:4284–86 [Google Scholar]
  33. Dean LE, Jones GT, MacDonald AG, Downham C, Sturrock RD, Macfarlane GJ. 33.  2014. Global prevalence of ankylosing spondylitis. Rheumatology. 53:4650–57 [Google Scholar]
  34. Evans DM, Spencer CCA, Pointon JJ, Su Z, Harvey D. 34.  et al. 2011. Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility. Nat. Genet. 43:8761–67 [Google Scholar]
  35. Cortes A, Hadler J, Pointon JP, Robinson PC. 35. Int. Genet. Ankyl. Spondylitis Consort. (IGAS) et al. 2013. Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci. Nat. Genet. 45:7730–38 [Google Scholar]
  36. Caffrey MF, James DC. 36.  1973. Human lymphocyte antigen association in ankylosing spondylitis. Nature 242:5393121 [Google Scholar]
  37. Schlosstein L, Terasaki PI, Bluestone R, Pearson CM. 37.  1973. High association of AN HL-A antigen, W27, with ankylosing spondylitis. N. Engl. J. Med. 288:14704–6 [Google Scholar]
  38. Brewerton DA, Caffrey M, Nicholls A, Walters D, Oates JK, James DC. 38.  1973. Reiter's disease and HL-A 27. Lancet 302:7836996–98 [Google Scholar]
  39. Stolwijk C, van Tubergen A, Castillo-Ortiz JD, Boonen A. 39.  2015. Prevalence of extra-articular manifestations in patients with ankylosing spondylitis: a systematic review and meta-analysis. Ann. Rheum. Dis. 74165–73
  40. Brewerton DA, Caffrey M, Nicholls A, Walters D, James DC. 40.  1973. Acute anterior uveitis and HL-A 27. Lancet 302:7836994–96 [Google Scholar]
  41. Brown MA, Pile KD, Kennedy LG, Calin A, Darke C. 41.  et al. 1996. HLA class I associations of ankylosing spondylitis in the white population in the United Kingdom. Ann. Rheum. Dis. 55:4268–70 [Google Scholar]
  42. Khan MA. 42.  2013. Polymorphism of HLA-B27: 105 subtypes currently known. Curr. Rheumatol. Rep. 15:10362 [Google Scholar]
  43. Liu Y, Jiang L, Cai Q, Danoy P, Barnardo MCNM. 43.  et al. 2010. Predominant association of HLA-B*2704 with ankylosing spondylitis in Chinese Han patients. Tissue Antigens 75:161–64 [Google Scholar]
  44. López-Larrea C, Sujirachato K, Mehra NK, Chiewsilp P, Isarangkura D. 44.  et al. 1995. HLA-B27 subtypes in Asian patients with ankylosing spondylitis: Evidence for new associations. Tissue Antigens 45:3169–76 [Google Scholar]
  45. D'Amato M, Fiorillo MT, Carcassi C, Mathieu A, Zuccarelli A. 45.  et al. 1995. Relevance of residue 116 of HLA-B27 in determining susceptibility to ankylosing spondylitis. Eur. J. Immunol. 25:113199–201 [Google Scholar]
  46. Fiorillo MT, Meadows L, D'Amato M, Shabanowitz J, Hunt DF. 46.  et al. 1997. Susceptibility to ankylosing spondylitis correlates with the C-terminal residue of peptides presented by various HLA-B27 subtypes. Eur. J. Immunol. 27:2368–73 [Google Scholar]
  47. García-Peydró M, Martí M, López de Castro JA. 47.  1999. High T cell epitope sharing between two HLA-B27 subtypes (B*2705 and B*2709) differentially associated to ankylosing spondylitis. J. Immunol. 163:42299–305 [Google Scholar]
  48. Hülsmeyer M, Fiorillo MT, Bettosini F, Sorrentino R, Saenger W. 48.  et al. 2004. Dual, HLA-B27 subtype-dependent conformation of a self-peptide. J. Exp. Med. 199:2271–81 [Google Scholar]
  49. Benjamin R, Parham P. 49.  1990. Guilt by association: HLA-B27 and ankylosing spondylitis. Immunol. Today 11:4137–42 [Google Scholar]
  50. Benjamin RJ, Madrigal JA, Parham P. 50.  1991. Peptide binding to empty HLA-B27 molecules of viable human cells. Nature 351:632174–77 [Google Scholar]
  51. Hermann E, Yu DT, Meyer zum Büschenfelde KH, Fleischer B. 51.  1993. HLA-B27-restricted CD8 T cells derived from synovial fluids of patients with reactive arthritis and ankylosing spondylitis. Lancet 342:8872646–50 [Google Scholar]
  52. Appel H, Kuon W, Kuhne M, Wu P, Kuhlmann S. 52.  et al. 2004. Use of HLA-B27 tetramers to identify low-frequency antigen-specific T cells in Chlamydia-triggered reactive arthritis. Arthritis Res. Ther. 6:6R521–34 [Google Scholar]
  53. Fiorillo MT, Maragno M, Butler R, Dupuis ML, Sorrentino R. 53.  2000. CD8+ T-cell autoreactivity to an HLA-B27-restricted self-epitope correlates with ankylosing spondylitis. J. Clin. Investig. 106:147–53 [Google Scholar]
  54. Allen RL, Gillespie GM, Hall F, Edmonds S, Hall MA. 54.  et al. 1997. Multiple T cell expansions are found in the blood and synovial fluid of patients with reactive arthritis. J. Rheumatol. 24:91750–57 [Google Scholar]
  55. May E, Dulphy N, Frauendorf E, Duchmann R, Bowness P. 55.  et al. 2002. Conserved TCR β chain usage in reactive arthritis; evidence for selection by a putative HLA-B27-associated autoantigen. Tissue Antigens 60:4299–308 [Google Scholar]
  56. Mamedov IZ, Britanova OV, Chkalina AV, Staroverov DB, Amosova AL. 56.  et al. 2009. Individual characterization of stably expanded T cell clones in ankylosing spondylitis patients. Autoimmunity 42:6525–36 [Google Scholar]
  57. May E, Dorris ML, Satumtira N, Iqbal I, Rehman MI. 57.  et al. 2003. CD8αβ T cells are not essential to the pathogenesis of arthritis or colitis in HLA-B27 transgenic rats. J. Immunol. 170:21099–105 [Google Scholar]
  58. Taurog JD, Dorris ML, Satumtira N, Tran TM, Sharma R. 58.  et al. 2009. Spondylarthritis in HLA-B27/human β2-microglobulin-transgenic rats is not prevented by lack of CD8. Arthritis Rheumatol. 60:71977–84 [Google Scholar]
  59. Sherlock JP, Joyce-Shaikh B, Turner SP, Chao C-C, Sathe M. 59.  et al. 2012. Il-23 induces spondyloarthropathy by acting on ROR-γt+ CD3+CD4CD8 entheseal resident T cells. Nat. Med. 18:71069–76 [Google Scholar]
  60. Allen RL, O'Callaghan CA, McMichael AJ, Bowness P. 60.  1999. Cutting edge: HLA-B27 can form a novel β2-microglobulin-free heavy chain homodimer structure. J. Immunol. 162:95045–48 [Google Scholar]
  61. Mear JP, Schreiber KL, Münz C, Zhu X, Stevanović S. 61.  et al. 1999. Misfolding of HLA-B27 as a result of its B pocket suggests a novel mechanism for its role in susceptibility to spondyloarthropathies. J. Immunol. 163:126665–70 [Google Scholar]
  62. Antoniou AN, Ford S, Taurog JD, Butcher GW, Powis SJ. 62.  2004. Formation of HLA-B27 homodimers and their relationship to assembly kinetics. J. Biol. Chem. 279:108895–902 [Google Scholar]
  63. Turner MJ, Delay ML, Bai S, Klenk E, Colbert RA. 63.  2007. HLA-B27 up-regulation causes accumulation of misfolded heavy chains and correlates with the magnitude of the unfolded protein response in transgenic rats: implications for the pathogenesis of spondylarthritis-like disease. Arthritis Rheumatol. 56:1215–23 [Google Scholar]
  64. DeLay ML, Turner MJ, Klenk EI, Smith JA, Sowders DP, Colbert RA. 64.  2009. HLA-B27 misfolding and the unfolded protein response augment interleukin-23 production and are associated with th17 activation in transgenic rats. Arthritis Rheumatol. 60:92633–43 [Google Scholar]
  65. Utriainen L, Firmin D, Wright P, Cerovic V, Breban M. 65.  et al. 2012. Expression of HLA-B27 causes loss of migratory dendritic cells in a rat model of spondylarthritis. Arthritis Rheumatol. 64:103199–209 [Google Scholar]
  66. Layh-Schmitt G, Yang EY, Kwon G, Colbert RA. 66.  2013. HLA-B27 alters the response to tumor necrosis factor α and promotes osteoclastogenesis in bone marrow monocytes from HLA-B27-transgenic rats. Arthritis Rheumatol. 65:82123–31 [Google Scholar]
  67. Goodall JC, Wu C, Zhang Y, McNeill L, Ellis L. 67.  et al. 2010. Endoplasmic reticulum stress-induced transcription factor, CHOP, is crucial for dendritic cell IL-23 expression. PNAS 107:4117698–703 [Google Scholar]
  68. Sahlberg AS, Ruuska M, Granfors K, Penttinen MA. 68.  2013. Altered regulation of ELAVL1/HuR in HLA-B27-expressing U937 monocytic cells. PLOS ONE 8:7e70377 [Google Scholar]
  69. Colbert RA, DeLay ML, Klenk EI, Layh-Schmitt G. 69.  2010. From HLA-B27 to spondyloarthritis: a journey through the ER. Immunol. Rev. 233:1181–202 [Google Scholar]
  70. Tran TM, Dorris ML, Satumtira N, Richardson JA, Hammer RE. 70.  et al. 2006. Additional human β2-microglobulin curbs HLA-B27 misfolding and promotes arthritis and spondylitis without colitis in male HLA-B27-transgenic rats. Arthritis Rheumatol. 54:41317–27 [Google Scholar]
  71. Campbell EC, Fettke F, Bhat S, Morley KD, Powis SJ. 71.  2011. Expression of MHC class I dimers and ERAP1 in an ankylosing spondylitis patient cohort. Immunology 133:3379–85 [Google Scholar]
  72. Ciccia F, Accardo-Palumbo A, Rizzo A, Guggino G, Raimondo S. 72.  et al. 2013. Evidence that autophagy, but not the unfolded protein response, regulates the expression of IL-23 in the gut of patients with ankylosing spondylitis and subclinical gut inflammation. Ann. Rheum. Dis. 73:1566–74 [Google Scholar]
  73. Dong W, Zhang Y, Yan M, Liu H, Chen Z, Zhu P. 73.  2008. Upregulation of 78-kDa glucose-regulated protein in macrophages in peripheral joints of active ankylosing spondylitis. Scand. J. Rheumatol. 37:6427–34 [Google Scholar]
  74. Bird LA, Peh CA, Kollnberger S, Elliott T, McMichael AJ, Bowness P. 74.  2003. Lymphoblastoid cells express HLA-B27 homodimers both intracellularly and at the cell surface following endosomal recycling. Eur. J. Immunol. 33:3748–59 [Google Scholar]
  75. Kollnberger S, Bird L, Sun M-Y, Retiere C, Braud VM. 75.  et al. 2002. Cell-surface expression and immune receptor recognition of HLA-B27 homodimers. Arthritis Rheumatol. 46:112972–82 [Google Scholar]
  76. Kollnberger S, Bird LA, Roddis M, Hacquard-Bouder C, Kubagawa H. 76.  et al. 2004. HLA-B27 heavy chain homodimers are expressed in HLA-B27 transgenic rodent models of spondyloarthritis and are ligands for paired Ig-like receptors. J. Immunol. 173:31699–710 [Google Scholar]
  77. Giles J, Shaw J, Piper C, Wong-Baeza I, McHugh K. 77.  et al. 2012. HLA-B27 homodimers and free H chains are stronger ligands for leukocyte Ig-like receptor B2 than classical HLA class I. J. Immunol. 188:126184–93 [Google Scholar]
  78. Wong-Baeza I, Ridley A, Shaw J, Hatano H, Rysnik O. 78.  et al. 2013. KIR3DL2 binds to HLA-B27 dimers and free H chains more strongly than other HLA class I and promotes the expansion of T cells in ankylosing spondylitis. J. Immunol. 190:73216–24 [Google Scholar]
  79. Chan AT, Kollnberger SD, Wedderburn LR, Bowness P. 79.  2005. Expansion and enhanced survival of natural killer cells expressing the killer immunoglobulin-like receptor KIR3DL2 in spondylarthritis. Arthritis Rheumatol. 52:113586–95 [Google Scholar]
  80. Bowness P, Ridley A, Shaw J, Chan AT, Wong-Baeza I. 80.  et al. 2011. Th17 cells expressing KIR3DL2+ and responsive to HLA-B27 homodimers are increased in ankylosing spondylitis. J. Immunol. 186:42672–80 [Google Scholar]
  81. Tsai WC, Chen CJ, Yen JH, Ou TT, Tsai JJ. 81.  et al. 2002. Free HLA class I heavy chain-carrying monocytes—a potential role in the pathogenesis of spondyloarthropathies. J. Rheumatol. 29:5966–72 [Google Scholar]
  82. Raine T, Brown D, Bowness P, Hill Gaston JS, Moffett A. 82.  et al. 2006. Consistent patterns of expression of HLA class I free heavy chains in healthy individuals and raised expression in spondyloarthropathy patients point to physiological and pathological roles. Rheumatology 45:111338–44 [Google Scholar]
  83. Stam NJ, Spits H, Ploegh HL. 83.  1986. Monoclonal antibodies raised against denatured HLA-B locus heavy chains permit biochemical characterization of certain HLA-C locus products. J. Immunol. 137:72299–306 [Google Scholar]
  84. Payeli SK, Kollnberger S, Marroquin Belaunzaran O, Thiel M, McHugh K. 84.  et al. 2012. Inhibiting HLA-B27 homodimer-driven immune cell inflammation in spondylarthritis. Arthritis Rheumatol. 64:103139–49 [Google Scholar]
  85. Van Praet L, Van den Bosch FE, Jacques P, Carron P, Jans L. 85.  et al. 2013. Microscopic gut inflammation in axial spondyloarthritis: a multiparametric predictive model. Ann. Rheum. Dis. 72:3414–17 [Google Scholar]
  86. Lin P, Bach M, Asquith M, Lee AY, Akileswaran L. 86.  et al. 2014. HLA-B27 and human β2-microglobulin affect the gut microbiota of transgenic rats. PLOS ONE 9:8e105684 [Google Scholar]
  87. Luthra-Guptasarma M, Singh B. 87.  2004. HLA-B27 lacking associated β2-microglobulin rearranges to auto-display or cross-display residues 169–181: a novel molecular mechanism for spondyloarthropathies. FEBS Lett. 575:1–31–8 [Google Scholar]
  88. Uchanska-Ziegler B, Ziegler A. 88.  2003. Ankylosing spondylitis: a β2m-deposition disease?. Trends Immunol. 24:273–76 [Google Scholar]
  89. Kievits F, Ivanyi P, Krimpenfort P, Berns A, Ploegh HL. 89.  1987. HLA-restricted recognition of viral antigens in HLA transgenic mice. Nature 329:6138447–49 [Google Scholar]
  90. Khare SD, Hansen J, Luthra HS, David CS. 90.  1996. HLA-B27 heavy chains contribute to spontaneous inflammatory disease in B27/human β2-microglobulin (β2m) double transgenic mice with disrupted mouse β2m. J. Clin. Investig. 98:122746–55 [Google Scholar]
  91. Kingsbury DJ, Mear JP, Witte DP, Taurog JD, Roopenian DC, Colbert RA. 91.  2000. Development of spontaneous arthritis in β2-microglobulin–deficient mice without expression of HLA-B27: association with deficiency of endogenous major histocompatibility complex class I expression. Arthritis Rheumatol. 43:102290–96 [Google Scholar]
  92. Hammer RE, Maika SD, Richardson JA, Tang JP, Taurog JD. 92.  1990. Spontaneous inflammatory disease in transgenic rats expressing HLA-B27 and human β2m: an animal model of HLA-B27-associated human disorders. Cell 63:51099–112 [Google Scholar]
  93. Breban M, Hammer RE, Richardson JA, Taurog JD. 93.  1993. Transfer of the inflammatory disease of HLA-B27 transgenic rats by bone marrow engraftment. J. Exp. Med. 178:51607–16 [Google Scholar]
  94. Zhou M, Sayad A, Simmons WA, Jones RC, Maika SD. 94.  et al. 1998. The specificity of peptides bound to human histocompatibility leukocyte antigen (HLA)-B27 influences the prevalence of arthritis in HLA-B27 transgenic rats. J. Exp. Med. 188:5877–86 [Google Scholar]
  95. Strange A, Capon F, Spencer CCA, Knight J. 95. Genet. Anal. Psoriasis Consort. Wellcome Trust Case Control Consort. 2 et al. 2010. A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1. Nat. Genet. 42:11985–90 [Google Scholar]
  96. Kirino Y, Bertsias G, Ishigatsubo Y, Mizuki N, Tugal-Tutkun I. 96.  et al. 2013. Genome-wide association analysis identifies new susceptibility loci for Behçet's disease and epistasis between HLA-B*51 and ERAP1. Nat. Genet. 45:2202–7 [Google Scholar]
  97. Kochan G, Krojer T, Harvey D, Fischer R, Chen L. 97.  et al. 2011. Crystal structures of the endoplasmic reticulum aminopeptidase-1 (ERAP1) reveal the molecular basis for N-terminal peptide trimming. PNAS 108:197745–50 [Google Scholar]
  98. Campbell EC, Fettke F, Bhat S, Morley KD, Powis SJ. 98.  2011. Expression of MHC class I dimers and ERAP1 in an ankylosing spondylitis patient cohort. Immunology 133:3379–85 [Google Scholar]
  99. Kanaseki T, Blanchard N, Hammer GE, Gonzalez F, Shastri N. 99.  2006. ERAAP synergizes with MHC class I molecules to make the final cut in the antigenic peptide precursors in the endoplasmic reticulum. Immunity 25:5795–806 [Google Scholar]
  100. Seregin SS, Rastall DPW, Evnouchidou I, Aylsworth CF, Quiroga D. 100.  et al. 2013. Endoplasmic reticulum aminopeptidase-1 alleles associated with increased risk of ankylosing spondylitis reduce HLA-B27 mediated presentation of multiple antigens. Autoimmunity 46:8497–508 [Google Scholar]
  101. Hammer GE, Gonzalez F, James E, Nolla H, Shastri N. 101.  2007. In the absence of aminopeptidase ERAAP, MHC class I molecules present many unstable and highly immunogenic peptides. Nat. Immunol. 8:1101–8 [Google Scholar]
  102. Chen L, Fischer R, Peng Y, Reeves E, McHugh K. 102.  et al. 2014. Critical role of endoplasmic reticulum aminopeptidase 1 in determining the length and sequence of peptides bound and presented by HLA-B27. Arthritis Rheumatol. 66:2284–94 [Google Scholar]
  103. Kenna TJ, Lau MC, Keith P, Ciccia F, Costello M-E. 103.  et al. 2015. Disease-associated polymorphisms in ERAP1 do not alter endoplasmic reticulum stress in patients with ankylosing spondylitis. Genes Immun. 16135–42
  104. Haroon N, Tsui FW, Uchanska-Ziegler B, Ziegler A, Inman RD. 104.  2012. Endoplasmic reticulum aminopeptidase 1 (ERAP1) exhibits functionally significant interaction with HLA-B27 and relates to subtype specificity in ankylosing spondylitis. Ann. Rheum. Dis. 71:4589–95 [Google Scholar]
  105. Zervoudi E, Saridakis E, Birtley JR, Seregin SS, Reeves E. 105.  et al. 2013. Rationally designed inhibitor targeting antigen-trimming aminopeptidases enhances antigen presentation and cytotoxic T-cell responses. PNAS 110:4919890–95 [Google Scholar]
  106. Brewerton DA, Caffrey M, Nicholls A, Walters D, James DC. 106.  1974. HL-A 27 and arthropathies associated with ulcerative colitis and psoriasis. Lancet 1:7864956–58 [Google Scholar]
  107. Thomson W, Barrett JH, Donn R, Pepper L, Kennedy LJ. 107.  et al. 2002. Juvenile idiopathic arthritis classified by the ILAR criteria: HLA associations in UK patients. Rheumatology 41:101183–89 [Google Scholar]
  108. Kanga U, Mehra NK, Larrea CL, Lardy NM, Kumar A, Feltkamp TE. 108.  1996. Seronegative spondyloarthropathies and HLA-B27 subtypes: a study in Asian Indians. Clin. Rheumatol. 15:Suppl. 113–18 [Google Scholar]
  109. Hill AV, Allsopp CE, Kwiatkowski D, Anstey NM, Greenwood BM, McMichael AJ. 109.  1991. HLA class I typing by PCR: HLA-B27 and an African B27 subtype. Lancet 337:8742640–42 [Google Scholar]
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