HLAB27 may present arthritogenic peptides

In addition to serving as a direct mediator of disease via inefficient folding and inappropriate dimerization, it has also been suggested that HLA-B27 may precipitate spondyloarthropathy by presenting arthritogenic peptides. The fact that the environment in which mice transgenic for HLA-B27 are raised affects arthritis incidence suggests that presentation of bacterial antigens may play a role in HLA-B27-medi-ated disease. Most of the rodent-based experiments involving bacterial peptides and HLA-B27 have been performed using an HLA-B27 transgenic rat model that is dependent upon P2m expression. Using LEW rats transgenic for HLA-B27 and human P2m, Popov et al. found that when the rats were immunized against HLA-B27 and restimulated in vitro with Chlamydia infected B27+ cells, CTL developed to both B27+ targets as well as Chlamydia infected syngeneic targets [63, 64]. These data indicated that CTLs were generated that recognize both HLA-B27 and

Chlamydia, implicating "a dynamic relationship between recognition of B27 peptides and Chlamydia peptides", although evidence of cross recognition of peptides is still lacking [63].

HLA-B27 animal models have also been useful for the study of other candidate antigens for AS, including autologous proteins such as the cartilage protein aggre-can. Using HLA-B27 transgenic mice immunized with human aggrecan peptides, Kuon et al. found that CD8+ T-cells from these mice were stimulated only by the human peptides and not by their murine counterparts [65]. The relevance of this murine HLA-B27 transgenic model is supported by a clinical study performed by Atagunduz et al. who found that CD8+ T-cells from synovial fluid and blood mononuclear cells from HLA-B27+ AS patients could be stimulated by cartilage antigens [66].

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