Advertisement

Biochemical Features of HLA-B27 and Antigen Processing

  • Simon J. Powis
  • Susana G. Santos
  • Antony N. Antoniou
Part of the Advances in Experimental Medicine and Biology book series (volume 649)

Abstract

The strong association of the human MHC class I allele HLA-B27 with the development of the chronic inflammatory disease ankylosing spondylitis (AS) is clear and has been known for over three decades. Despite this, it is far from clear how HLA-B27 is directly involved in AS. In recent years considerable progress has been made in defining the assembly pathway and the protein components involved in successfully folding MHC class I molecules in the environment of the endoplasmic reticulum. This process involves a number of critical interactions, which may influence how HLA-B27 molecules fold and what peptides become loaded. The impact of the unpaired Cys-67 residue in the peptide-binding groove upon the behaviour of both correctly folded and misfolded HLA-B27 molecules, especially its ability to allow the formation of B27 heavy-chain oligomers or dimers, which may form novel targets for immune receptors, or be an indicator of intracellular stress, has also been the focus of much research. In this chapter we aim to review recent data to determine whether any biochemical features of HLA-B27 can supply clues as to its enigmatic role in AS and will also comment on future potential directions of biochemical research into HLA-B27.

Keywords

Ankylose Spondylitis Heavy Chain Transporter Associate With Antigen Processing Conserve Disulfide Bond Mouse Major Histocompatibility Complex Class 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Ramos M, Paradela A, Vazquez M et al. Differential association of HLA-B*2705 and B*2709 to ankylosing spondylitis correlates with limited peptide subsets but not with altered cell surface stability. J Biol Chem 2002; 277(32):28749–28756.PubMedCrossRefGoogle Scholar
  2. 2.
    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):5543–5547.PubMedGoogle Scholar
  3. 3.
    Kollnberger S, Bird L, Sun MY et al. Cell-surface expression and immune receptor recognition of HLA-B27 homodimers. Arthritis Rheum 2002; 46(11):2972–2982.PubMedCrossRefGoogle Scholar
  4. 4.
    Degen E, Williams DB. Participation of a novel 88-kD protein in the biogenesis of murine class I histocompatibility molecules. J Cell Biol 1991; 112(6):1099–1115.PubMedCrossRefGoogle Scholar
  5. 5.
    Nossner E, Parham P. Species-specific differences in chaperone interaction of human and mouse major histocompatibility complex class I molecules. J Exp Med 1995; 181(1):327–337.PubMedCrossRefGoogle Scholar
  6. 6.
    Sadasivan B, Lehner PJ, Ortmann B et al. Roles for calreticulin and a novel glycoprotein, tapasin, in the interaction of MHC class I molecules with TAP. Immunity 1996; 5(2):103–114.PubMedCrossRefGoogle Scholar
  7. 7.
    Antoniou AN, Powis SJ, Elliott T. Assembly and export of MHC class I peptide ligands. Curr Opin Immunol 2003; 15(1):75–81.PubMedCrossRefGoogle Scholar
  8. 8.
    Hughes EA, Cresswell P. The thiol oxidoreductase ERp57 is a component of the MHC class I peptide-loading complex. Curr Biol 1998; 8(12):709–712.PubMedCrossRefGoogle Scholar
  9. 9.
    Lindquist JA, Jensen ON, Mann M et al. ER-60, a chaperone with thiol-dependent reductase activity involved in MHC class I assembly. Embo J 1998; 17(8):2186–2195.PubMedCrossRefGoogle Scholar
  10. 10.
    Morrice NA, Powis SJ. A role for the thiol-dependent reductase ERp57 in the assembly of MHC class I molecules. Curr Biol 1998; 8(12):713–716.PubMedCrossRefGoogle Scholar
  11. 11.
    Ortmann B, Androlewicz MJ, Cresswell P. MHC class I/beta 2-microglobulin complexes associate with TAP transporters before peptide binding. Nature 1994; 368(6476):864–867.PubMedCrossRefGoogle Scholar
  12. 12.
    Ortmann B, Copeman J, Lehner PJ et al. A critical role for tapasin in the assembly and function of multimeric MHC class I-TAP complexes. Science 1997; 277(5330):1306–1309.PubMedCrossRefGoogle Scholar
  13. 13.
    Park B, Lee S, Kim E et al. Redox regulation facilitates optimal peptide selection by MHC class I during antigen processing. Cell 2006; 127(2):369–382.PubMedCrossRefGoogle Scholar
  14. 14.
    Williams AP, Peh CA, Purcell AW et al. Optimization of the MHC class I peptide cargo is dependent on tapasin. Immunity 2002; 16(4):509–520.PubMedCrossRefGoogle Scholar
  15. 15.
    Kienast A, Preuss M, Winkler M et al. Redox regulation of peptide receptivity of major histocompatibility complex class I molecules by ERp57 and tapasin. Nat Immunol 2007; 8(8):864–872.PubMedCrossRefGoogle Scholar
  16. 16.
    Santos SG, Campbell EC, Lynch S et al. Major histocompatibility complex class I-ERp57-tapasin interactions within the peptide-loading complex. J Biol Chem 2007; 282(24):17587–17593.PubMedCrossRefGoogle Scholar
  17. 17.
    Wearsch PA, Cresswell P. Selective loading of high-affinity peptides onto major histocompatibility complex class I molecules by the tapasin-ERp57 heterodimer. Nat Immunol 2007; 8(8):873–881.PubMedCrossRefGoogle Scholar
  18. 18.
    Park B, Lee S, Kim E et al. A single polymorphic residue within the peptide-binding cleft of MHC class I molecules determines spectrum of tapasin dependence. J Immunol 2003; 170(2):961–968.PubMedGoogle Scholar
  19. 19.
    Sesma L, Galocha B, Vazquez M et al. Qualitative and quantitative differences in peptides bound to HLA-B27 in the presence of mouse versus human tapasin define a role for tapasin as a size-dependent peptide editor. J Immunol 2005; 174(12):7833–7844.PubMedGoogle Scholar
  20. 20.
    Tourdot S, Gould KG. Competition between MHC class I alleles for cell surface expression alters CTL responses to influenza A virus. J Immunol 2002; 169(10):5615–5621.PubMedGoogle Scholar
  21. 21.
    Tourdot S, Nejmeddine M, Powis SJ et al. Different MHC class I heavy chains compete with each other for folding independently of beta 2-microglobulin and peptide. J Immunol 2005; 174(2):925–933.PubMedGoogle Scholar
  22. 22.
    Allen RL, O’Callaghan CA, McMichael AJ et al. Cutting edge: HLA-B27 can form a novel beta 2-microglobulin-free heavy chain homodimer structure. J Immunol 1999; 162(9):5045–5048.PubMedGoogle Scholar
  23. 23.
    Antoniou AN, Ford S, Taurog JD et al. Formation of HLA-B27 homodimers and their relationship to assembly kinetics. J Biol Chem 2004; 279(10):8895–8902.PubMedCrossRefGoogle Scholar
  24. 24.
    Lemin AJ, Saleki K, van Lith M et al. Activation of the unfolded protein response and alternative splicing of ATF6alpha in HLA-B27 positive lymphocytes. FEBS Lett 2007; 581(9):1819–1824.PubMedCrossRefGoogle Scholar
  25. 25.
    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(3):748–759.PubMedCrossRefGoogle Scholar
  26. 26.
    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):1699–1710.PubMedGoogle Scholar
  27. 27.
    Tran TM, Satumtira N, Dorris ML et al. HLA-B27 in transgenic rats forms disulfide-linked heavy chain oligomers and multimers that bind to the chaperone BiP. J Immunol 2004; 172(8):5110–5119.PubMedGoogle Scholar
  28. 28.
    Turner MJ, Sowders DP, DeLay ML et al. HLA-B27 misfolding in transgenic rats is associated with activation of the unfolded protein response. J Immunol 2005; 175(4):2438–2448.PubMedGoogle Scholar
  29. 29.
    Taurog JD, Maika SD, Satumtira N et al. Inflammatory disease in HLA-B27 transgenic rats. Immunol Rev 1999;169:209–223.PubMedCrossRefGoogle Scholar
  30. 30.
    Santos SG, Antoniou AN, Sampaio P et al. Lack of tyrosine 320 impairs spontaneous endocytosis and enhances release of HLA-B27 molecules. J Immunol 2006; 176(5):2942–2949.PubMedGoogle Scholar
  31. 31.
    Tsai WC, Chen CJ, Yen JH et al. Free HLA class I heavy chain-carrying monocytes—a potential role in the pathogenesis of spondyloarthropathies. J Rheumatol 2002; 29(5):966–972.PubMedGoogle Scholar
  32. 32.
    Stam NJ, Spits H, Ploegh HL. Monoclonal antibodies raised against denatured HLA-B locus heavy chains permit biochemical characterization of certain HLA-C locus products. J Immunol 1986; 137(7):2299–2306.PubMedGoogle Scholar
  33. 33.
    Perosa F, Luccarelli G, Prete M et al. Beta 2-microglobulin-free HLA class I heavy chain epitope mimicry by monoclonal antibody HC-10-specific peptide. J Immunol 2003; 171(4):1918–1926.PubMedGoogle Scholar
  34. 34.
    Archer JR, Whelan MA, Badakere SS et al. Effect of a free sulphydryl group on expression of HLA-B27 specificity. Scand J Rheumatol 1990; 87(Suppl):44–50.CrossRefGoogle Scholar
  35. 35.
    MacLean L, Macey M, Lowdell M et al. Sulphydryl reactivity of the HLA-B27 epitope: accessibility of the free cysteine studied by flow cytometry. Ann Rheum Dis 1992; 51(4):456–460.PubMedCrossRefGoogle Scholar
  36. 36.
    Whelan MA, Archer JR. Chemical reactivity of an HLA-B27 thiol group. Eur J Immunol 1993; 23(12):3278–3285.PubMedCrossRefGoogle Scholar
  37. 37.
    Hacquard-Bouder C, Chimenti MS, Giquel B et al. Alteration of antigen-independent immunologic synapse formation between dendritic cells from HLA-B27-transgenic rats and CD4+ T-cells: selective impairment of costimulatory molecule engagement by mature HLA-B27. Arthritis Rheum 2007; 56(5):1478–1489.PubMedCrossRefGoogle Scholar
  38. 38.
    Ackerman AL, Cresswell P. Regulation of MHC class I transport in human dendritic cells and the dendritic-like cell line KG-1. J Immunol 2003; 170(8):4178–4188.PubMedGoogle Scholar
  39. 39.
    MacAry PA, Lindsay M, Scott MA et al. Mobilization of MHC class I molecules from late endosomes to the cell surface following activation of CD34-derived human Langerhans cells. Proc Natl Acad Sci USA 2001; 98(7):3982–3987.PubMedCrossRefGoogle Scholar
  40. 40.
    Guermonprez P, Saveanu L, Kleijmeer M et al. ER-phagosome fusion defines an MHC class I cross-presentation compartment in dendritic cells. Nature 2003; 425(6956):397–402.PubMedCrossRefGoogle Scholar
  41. 41.
    Houde M, Bertholet S, Gagnon E et al. Phagosomes are competent organelles for antigen cross-presentation. Nature 2003; 425(6956):402–406.PubMedCrossRefGoogle Scholar
  42. 42.
    Ackerman AL, Kyritsis C, Tampe R et al. Access of soluble antigens to the endoplasmic reticulum can explain cross-presentation by dendritic cells. Nat Immunol 2005; 6(1):107–113.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2009

Authors and Affiliations

  • Simon J. Powis
    • 1
  • Susana G. Santos
    • 1
  • Antony N. Antoniou
    • 1
  1. 1.Bute Medical SchoolUniversity of St AndrewsFifeScotland, UK

Personalised recommendations