title: The biochemistry and immunology of non-canonical forms of HLA-B27.
abstract: HLA-B27 (B27) is strongly associated with the spondyloarthritides. B27 is expressed at the cell surface of antigen presenting cells (APC) both as canonical β2m-associated and non-canonical β2m-free heavy chain (FHC) forms which include B27 dimers (termed B272). B27 FHC forms arise in an endosomal compartment from recycling β2m-associated B27. Formation of cell surface FHC dimers is critically dependent on an unpaired reactive cysteine 67 in the α1 helix of the class I heavy chain. HLA-B27 also form redox-inducible β2m-associated dimers on exosomes and apoptosing cells. By contrast with cell surface expressed cysteine 67-dependent heavy chain dimers these dimers are dependent on a cytoplasmic cysteine 325 for their formation. HLA-B27 binds to immunoregulatory receptors including members of the Killer cell Immunoglobulin-like (KIR) and Leukocyte Immunoglobulin-like receptor family. B27 FHC bind to different but overlapping sets of these immunoreceptors compared to classical β2m-associated HLA-B27. B27 FHC bind more strongly to KIR3DL2 and LILRB2 immune receptor than other β2m-associated HLA-class I ligands. Genetic studies have implicated genes which control production of the important proinflammatory cytokine IL-17 in the pathogenesis of spondyloarthritis. Cell surface HLA-B27 FHC binding to these immune receptors or acting through other mechanisms could impact on the pathogenesis of spondyloarthritis by promoting immune cell production of IL-17. Here we review the literature on these non-canonical forms of HLA-B27 and the immune receptors they bind to and discuss the possible relevance of these interactions to the pathogenesis of spondyloarthropathy.
authors.affiliation: Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Nuffield Orthopaedic Centre, Oxford University, Windmill Road, Oxford OX3 7LD, United Kingdom.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Shaw
authors.forename: Hiroko
authors.initials: H
authors.lastname: Hatano
authors.forename: Simon
authors.initials: S
authors.lastname: Kollnberger
mesh_terms: D000954:Antigens, Surface / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D015796:HLA-B27 Antigen / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000378:metabolism*; D017433:Protein Structure, Secondary; D011971:Receptors, Immunologic / Q000378:metabolism*; D054347:Receptors, KIR3DL2 / Q000378:metabolism*; D013167:Spondylitis, Ankylosing / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*
chemical_list: D000954:Antigens, Surface; D015796:HLA-B27 Antigen; D020381:Interleukin-17; C515084:KIR3DL2 protein, human; C491341:LILRB2 protein, human; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D054347:Receptors, KIR3DL2
keywords: HLA-B27; IL-17; IL-23 receptor; KIR3DL2; LILRB2; Spondyloarthritis