Biochemical features of HLA-B27 and antigen processing.

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 o the unpaired Cys-67 residue in the peptide-binding groove upon the behaviour of both correctl 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.

[1]  N. Morrice,et al.  A role for the thiol-dependent reductase ERp57 in the assembly of MHC class I molecules , 1998, Current Biology.

[2]  J. Archer,et al.  Chemical reactivity of an HLA‐B27 thiol group , 1993, European journal of immunology.

[3]  T. Elliott,et al.  Assembly and export of MHC class I peptide ligands. , 2003, Current opinion in immunology.

[4]  A. McMichael,et al.  Cell-surface expression and immune receptor recognition of HLA-B27 homodimers. , 2002, Arthritis and rheumatism.

[5]  H. Ploegh,et al.  Monoclonal antibodies raised against denatured HLA-B locus heavy chains permit biochemical characterization of certain HLA-C locus products. , 1986, Journal of immunology.

[6]  P. Cresswell,et al.  Regulation of MHC Class I Transport in Human Dendritic Cells and the Dendritic-Like Cell Line KG-11 , 2003, The Journal of Immunology.

[7]  P. Lehner,et al.  Mobilization of MHC class I molecules from late endosomes to the cell surface following activation of CD34-derived human Langerhans cells , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[8]  E. Degen,et al.  Participation of a novel 88-kD protein in the biogenesis of murine class I histocompatibility molecules , 1991, The Journal of cell biology.

[9]  P. Sampaio,et al.  Lack of Tyrosine 320 Impairs Spontaneous Endocytosis and Enhances Release of HLA-B27 Molecules , 2006, The Journal of Immunology.

[10]  F. Dammacco,et al.  β2-Microglobulin-Free HLA Class I Heavy Chain Epitope Mimicry by Monoclonal Antibody HC-10-Specific Peptide1 , 2003, The Journal of Immunology.

[11]  K. Gould,et al.  Competition Between MHC Class I Alleles for Cell Surface Expression Alters CTL Responses to Influenza A Virus1 , 2002, The Journal of Immunology.

[12]  P. Cresswell,et al.  Roles for calreticulin and a novel glycoprotein, tapasin, in the interaction of MHC class I molecules with TAP. , 1996, Immunity.

[13]  M. Mann,et al.  ER‐60, a chaperone with thiol‐dependent reductase activity involved in MHC class I assembly , 1998, The EMBO journal.

[14]  S. Riddell,et al.  Redox Regulation Facilitates Optimal Peptide Selection by MHC Class I during Antigen Processing , 2006, Cell.

[15]  P. Cresswell,et al.  The thiol oxidoreductase ERp57 is a component of the MHC class I peptide-loading complex , 1998, Current Biology.

[16]  Chung-Jen Chen,et al.  Free HLA class I heavy chain-carrying monocytes--a potential role in the pathogenesis of spondyloarthropathies. , 2002, The Journal of rheumatology.

[17]  R. Tampé,et al.  Access of soluble antigens to the endoplasmic reticulum can explain cross-presentation by dendritic cells , 2005, Nature Immunology.

[18]  A. McMichael,et al.  HLA-B27 Heavy Chain Homodimers Are Expressed in HLA-B27 Transgenic Rodent Models of Spondyloarthritis and Are Ligands for Paired Ig-Like Receptors1 , 2004, The Journal of Immunology.

[19]  Euijae Kim,et al.  A Single Polymorphic Residue Within the Peptide-Binding Cleft of MHC Class I Molecules Determines Spectrum of Tapasin Dependence1 , 2003, The Journal of Immunology.

[20]  M. Whelan,et al.  Effect of a free sulphydryl group on expression of HLA-B27 specificity. , 1990, Scandinavian journal of rheumatology. Supplement.

[21]  Michael J. Wilson,et al.  Cutting Edge: Leukocyte Receptor Complex-Encoded Immunomodulatory Receptors Show Differing Specificity for Alternative HLA-B27 Structures1 , 2001, The Journal of Immunology.

[22]  P. Parham,et al.  Species-specific differences in chaperone interaction of human and mouse major histocompatibility complex class I molecules , 1995, The Journal of experimental medicine.

[23]  A. Marina,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* , 2002, The Journal of Biological Chemistry.

[24]  R. Tampé,et al.  A critical role for tapasin in the assembly and function of multimeric MHC class I-TAP complexes. , 1997, Science.

[25]  S. Powis,et al.  Different MHC Class I Heavy Chains Compete with Each Other for Folding Independently of β2-Microglobulin and Peptide1 , 2005, The Journal of Immunology.

[26]  M. van Lith,et al.  Activation of the unfolded protein response and alternative splicing of ATF6α in HLA‐B27 positive lymphocytes , 2007, FEBS letters.

[27]  Etienne Gagnon,et al.  Phagosomes are competent organelles for antigen cross-presentation , 2003, Nature.

[28]  Elaine C. Campbell,et al.  Major Histocompatibility Complex Class I-ERp57-Tapasin Interactions within the Peptide-loading Complex* , 2007, Journal of Biological Chemistry.

[29]  R. Hammer,et al.  Inflammatory disease in HLA‐B27 transgenic rats , 1999, Immunological reviews.

[30]  M. Preuss,et al.  Redox regulation of peptide receptivity of major histocompatibility complex class I molecules by ERp57 and tapasin , 2007, Nature Immunology.

[31]  P. Cresswell,et al.  MHC class l/β2-microglobulin complexes associate with TAP transporters before peptide binding , 1994, Nature.

[32]  J. Taurog,et al.  HLA-B27 in Transgenic Rats Forms Disulfide-Linked Heavy Chain Oligomers and Multimers That Bind to the Chaperone BiP1 , 2004, The Journal of Immunology.

[33]  P. Cresswell,et al.  Selective loading of high-affinity peptides onto major histocompatibility complex class I molecules by the tapasin-ERp57 heterodimer , 2007, Nature Immunology.

[34]  J. Davoust,et al.  ER–phagosome fusion defines an MHC class I cross-presentation compartment in dendritic cells , 2003, Nature.

[35]  R. Colbert,et al.  HLA-B27 Misfolding in Transgenic Rats Is Associated with Activation of the Unfolded Protein Response1 , 2005, The Journal of Immunology.

[36]  M. Chimenti,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. , 2007, Arthritis and rheumatism.

[37]  T. Elliott,et al.  Lymphoblastoid cells express HLA‐B27 homodimers both intracellularly and at the cell surface following endosomal recycling , 2003, European journal of immunology.

[38]  James McCluskey,et al.  Optimization of the MHC class I peptide cargo is dependent on tapasin. , 2002, Immunity.

[39]  S. Powis,et al.  Formation of HLA-B27 Homodimers and Their Relationship to Assembly Kinetics* , 2004, Journal of Biological Chemistry.

[40]  D. Perrett,et al.  Sulphydryl reactivity of the HLA-B27 epitope: accessibility of the free cysteine studied by flow cytometry. , 1992, Annals of the rheumatic diseases.

[41]  J. McCluskey,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 Editor1 , 2005, The Journal of Immunology.

[42]  A. McMichael,et al.  Cutting edge: HLA-B27 can form a novel beta 2-microglobulin-free heavy chain homodimer structure. , 1999, Journal of immunology.