Immunology, genetics, and animal models of the spondyloarthropathies

Over the past few years, the association of HLA-B27 with inflammatory disease has attracted increasing attention from basic and clinical investigators. To some extent, this is due to advances in basic immunology that permit the generation and experimental testing of hypotheses regarding the basic mechanisms underlying this association. The publication of information on the three-dimensional structure of the HLA-A2 molecule in 1987 can be viewed as a landmark in the understanding of the role of major histocompatibility complex (MHC) molecules in the immune response (Bjorkman et al., Nature 1987, 329:506-518), and the concept that T cells recognize intracellularly generated peptide antigens bound to the antigen-binding pocket of MHC molecules is now firmly established, although the biochemical mechanisms underlying the formation of the T-cell receptor-antigen-MHC complex remain to be elucidated. Other recent developments potentially relevant to the problem of B27 and disease include an increased appreciation of the role of heat-shock proteins in the immune response, delineation of some of the characteristics of the class of T cells bearing γδ T-cell receptors, and the emergence of transgenic animal technology as a powerful tool for examining MHC function. This review focuses on recent publications describing advances in basic immunology of potential relevance to the B27-disease association, as well as recent publications more specifically involving studies of B27 and B27-associated diseases. Most of the basic facts regarding the immunogenetics of HLA-B27 and disease were presented in the version of this review published 1 year ago (Taurog, Curr Opin Rheumatol 1989, 1:144-150). In addition, many other reviews on various aspects of these topics have appeared within the past year (Lopez de Castro, Immunol Today 1989, 10:239-246; Yu et al., Ann Intern Med 1989, 111:581-591; Mielants and Veys, J Rheumatol 1990, 17:7-10; Schwartz, Arthritis Rheum 1990, 33:457-465; Vaughan, Bull Rheum Dis 1990, 39:1-7). The reader new to this field should consult these reviews for background material.