Abstract
HLA-B27 (B27) is strongly associated with spondyloarthopathy. The classical role of B27 is to present peptides from intracellular pathogens as a heterotrimeric complex with β2 microglobulin for recognition by the T-cell receptor (TCR) of CD8 T-cells. In addition to heterotrimers, B27 can also be expressed as cell surface beta2-microglobulin (β2m)-free homodimers (B272). In addition to the TCR, MHC class I molecules bind to immunoregulatory receptors including members of the killer immunoglobulin-like receptor (KIR) and leukocyte immunoglobulin-like receptor (LILR) families. Rodents express the paired immunoglobulin receptor (PIR) family which are related to LILR. B272 but not β2m-associated B27 binds to KIR3DL2 and rodent PIR. NK and T-cells expressing the immune receptor KIR3DL2, which interacts with B272, are expanded in B27 AS patients. Ligation of immune receptors by B272 promotes the survival of KIR-expressing leukocytes and modulates immune cytokine production. Upregulation of B272 in spondyloarthritis and differential interaction of β2m-associated HLA-B27 and B272 with immune receptors could be involved in the pathogenesis of B27-associated spondyloarthritis (AS).
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Brown MA, Pile KD, Kennedy LG et al. HLA class I associations of ankylosing spondylitis in the white population in the United Kingdom. Annals Rheum Dis 1996; 55:268–270.
Allen RL, Bowness P. McMichael A. The role of HLA-B27 in spondyloarthritis. Immunogenetics 1999; 50:220–227.
Colmegna I, Cuchacovich R, Espinoza LR. HLA-B27-associated reactive arthritis: Pathogenetic and clinical considerations. Clin Microbiol Rev 2004; 17(2):348–69. Review.
May E, Dorris ML, Satumtira N et al. CD8 αβ T-cells are not essential to the pathogenesis of arthritis or colitis in HLA-B27 transgenic rats. J Immunol 2003; 170(2):1099–105.
Allen RL, O’Callaghan CA, McMichael AJ et al. 1999. Cutting edge: HLA-B27 can form a novel beta 2-microglobulin-free heavy chain homodimer structure. J Immunol 162:5045–5048.
Stam NJ, Vroom TM, Peters PJ et al. HLA-A-and HLA-B-specific monoclonal antibodies reactive with free heavy chains in western blots, in formalin-fixed, paraffin-embedded tissue sections and in cryo-immuno-electron microscopy. Int Immunol 1990; 2(2):113–25.
Raine T, Brown D, Bowness P et al. 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 (Oxford) 2006; 45(11):1338–44.
Tsai WC, Chen CJ, Yen J et al. Free HLA class I heavy chain-carrying monocytes—A potential role in the pathogenesis of spondyloarthropathies. J Rheumatol 2002; 29:966–972.
Lan CC, Tsai WC, Wu CS et al. Psoriatic patients with arthropathy show significant expression of free HLA class I heavy chains on circulating monocytes: A potential role in the pathogenesis of psoriatic arthropathy. Br J Dermatol 2004; 151(1):24–31.
Kollnberger S, Bird L, Sun MY et al. Cell-surface expression and immune receptor recognition of HLA-B27 homodimers. Arthritis Rheum 2002; 46(11):2972–82.
Bird LA, Peh CA, Kollnberger S et al. Lymphoblastoid cells express HLA-B27 homodimers both intracellularly and at the cell surface following endosomal recycling. Eur J Immunol 2003; 33:748–759.
Kollnberger S, Bird LA, Roddis M et al. 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 2004; 173(3):1699–710.
Kollnberger S, Chan A, Sun MY et al. Interaction of HLA-B27 homodimers with KIR3DL1 and KIR3DL2, unlike HLA-B27 heterotrimers, is independent of the sequence of bound peptide. Eur J Immunol 2007; 37(5):1313–22.
Zhou M, Sayad A, Simmons WA et al. 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 1998; 188(5):877–86.
Tran TM, Dorris ML, Satumtira N et al. Additional human beta2-microglobulin curbs HLA-B27 misfolding and promotes arthritis and spondylitis without colitis in male HLA-B27-transgenic rats. Arthritis Rheum 2006; 54(4):1317–27.
Boyson JE, Erskine R, Whitman MC et al. Disulfide bond-mediated dimerization of HLA-G on the cell surface. Proc Natl Acad Sci USA. 2002; 99(25):16180–5.
Apps R, Gardner L, Sharkey AM et al. A homodimeric complex of HLA-G on normal trophoblast cells modulates antigen-presenting cells via LILRB1. Eur J Immunol 2007; 37(7):1924–37.
Lanier LL. Follow the leader: NK cell receptors for classical and nonclassical MHC class I. Cell 1998; 92:705–707.
Colonna M, Nakajima H, Navarro F et al. A novel family of Ig-like receptors for HLA class I molecules that modulate function of lymphoid and myeloid cells. J Leukoc Biol 1999; 66(3):375–81. Review.
Takai T. Paired immunoglobulin-like receptors and their MHC class I recognition. Immunology 2005; 115(4):433–40. Review.
Diefenbach A, Raulet DH. Innate immune recognition by stimulatory immunoreceptors. Curr Opin Immunol 2003; 15(1):37–44. Review.
Vankayalapati R, Wizel B, Weis SE et al. The NKp46 receptor contributes to NK cell lysis of mononuclear phagocytes infected with an intracellular bacterium. J Immunol 2002; 168(7):3451–7.
Vilches C, Parham P. KIR: diverse, rapidly evolving receptors of innate and adaptive immunity. Annu Rev Immunol 2002; 20:217–51.
Yokoyama WM, Kim S. How do natural killer cells find self to achieve tolerance? Immunity 2006; 24(3):249–57. Review.
Goronzy JJ, Henel G, Sawai H et al. Costimulatory pathways in rheumatoid synovitis and T-cell senescence. Ann NY Acad Sci 2005; 1062:182–94. Review.
Young NT, Uhrberg M. KIR expression shapes cytotoxic repertoires: a developmental program of survival. Trends Immunol 2002; 23(2):71–5. Review.
Van Bergen J, Thompson A, van der Slik A et al. Phenotypic and functional characterization of CD4 T-cells expressing killer Ig-like receptors. J Immunol 2004; 173(11):6719–26.
Abedin S, Michel JJ, Lemster B et al. Diversity of NKR expression in aging T-cells and in T-cells of the aged: the new frontier into the exploration of protective immunity in the elderly. Mech Ageing Dev 2005; 126(6–7):722–31.
Ugolini S, Arpin C, Anfossi N et al. Involvement of inhibitory NKRs in the survival of a subset of memory-phenotype CD8+ T-cells. Nat Immunol 2001; 2:430–435.
Nelson GW, Martin MP, Gladman D et al. Cutting edge: heterozygote advantage in autoimmune disease: hierarchy of protection/susceptibility conferred by HLA and killer Ig-like receptor combinations in psoriatic arthritis. J Immunol 2004; 173(7):4273–6.
Ristich V, Liang S, Zhang W et al. Tolerization of dendritic cells by HLA-G. Eur J Immunol 2005; 35(4):1133–42.
Chang CC, Ciubotariu R, Manavalan JS et al. Tolerization of dendritic cells by T(S) cells: the crucial role of inhibitory receptors ILT3 and ILT4. Nat Immunol 2002; 3(3):215–7.
Allen RL, Raine T, Haude A et al. Leukocyte receptor complex-encoded immunomodulatory receptors show differing specificity for alternative HLA-B27 structures. J Immunol 2001; 167(10):5543–7.
Horuzsko A, Lenfant F, Munn DH et al. Maturation of antigen-presenting cells is compromised in HLA-G transgenic mice. Int Immunol 2001; 13(3):385–94.
Ujike A, Takeda K, Nakamura A et al. Impaired dendritic cell maturation and increased T(H)2 responses in PIR-B(-/-) mice. Nat Immunol 2002; 3(6):542–8.
Hacquard-Bouder C, Falgarone G, Bosquet A et al. Defective costimulatory function is a striking feature of antigen-presenting cells in an HLA-B27-transgenic rat model of spondylarthropathy. Arthritis Rheum 2004; 50(5):1624–35.
Liu J, Liu Z, Witkowski P et al. Rat CD8+FOXP3+ T suppressor cells mediate tolerance to allogeneic heart transplants, inducing PIR-B in APC and rendering the graft invulnerable to rejection. Transpl Immunol 2004; 13(4):239–47.
Chan AT, Kollnberger SD, Wedderburn LR et al. Expansion and enhanced survival of natural killer cells expressing the killer immunoglobulin-like receptor KIR3DL2 in spondylarthritis. Arthritis Rheum 2005; 52(11):3586–95.
Duftner C, Goldberger C, Falkenbach A et al. Prevalence, clinical relevance and characterization of circulating cytotoxic CD4+CD28-T-cells in ankylosing spondylitis. Arthritis Res Ther 2003; 5(5):R292–300.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2009 Landes Bioscience and Springer Science+Business Media
About this chapter
Cite this chapter
Kollnberger, S., Bowness, P. (2009). The Role of B27 Heavy Chain Dimer Immune Receptor Interactions in Spondyloarthritis. In: López-Larrea, C., Díaz-Peña, R. (eds) Molecular Mechanisms of Spondyloarthropathies. Advances in Experimental Medicine and Biology, vol 649. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0298-6_21
Download citation
DOI: https://doi.org/10.1007/978-1-4419-0298-6_21
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4419-0297-9
Online ISBN: 978-1-4419-0298-6
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)