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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. β2m-free B27 heavy chain structures including homodimers (B272) can also be expressed at the cell surface following endosomal recycling of cell surface heterotrimers. Cell surface free heavy chains and B272 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.

Original publication

DOI

10.1146/annurev-immunol-032414-112110

Type

Journal article

Journal

Annual review of immunology

Publication Date

01/2015

Volume

33

Pages

29 - 48

Addresses

Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Science (NDORMS), Botnar Research Center, University of Oxford, Headington, Oxford OX3 9DL, United Kingdom; email: Paul.bowness@ndorms.ox.ac.uk.

Keywords

Animals, Humans, Spondylarthropathies, HLA-B27 Antigen