Breaking the rules: The unconventional recognition of HLA-B27 by CD4+ T lymphocytes as an insight into the pathogenesis of the spondyloarthropathies

Abstract

Despite extensive research, it remains unclear why a small proportion of HLA-B27+ individuals develop spondyloarthropathies (SpA). Because the function of HLA-B27, as a major histocompatibility complex (MHC) class I molecule, is peptide presentation to CD8+ T cells, research has concentrated on the role of HLA-B27 as a restriction element for CD8+ cytotoxic T lymphocytes in pathogenesis. However, findings in the B27-transgenic animal models, together with the identification of unusual processing and presentation features of HLA-B27, have raised alternative hypotheses for the pathogenic role of HLA-B27. One such hypothesis is that HLA-B27 can be recognized by CD4+ T lymphocytes. Here we report the identification of such unusual cells, which break the conventional rules of MHC restriction, and propose a model for the role of such CD4+ T cells in SpA.