Peptides derived from amino acid sequence 60-80 of
HLA-B27 (B27PA, aa 60-72 and B2702PA, aa 60-80) mimic
cytokeratin and are able to induce in vitro proliferation of human peripheral blood lymphocytes as well as
arthritis in Lewis rats. Here we show that the pathogenic
epitope recognized by autoaggressive rat T cells is located at the N-terminus of the sequence, between aa 60 and 72. A C-terminally elongated 25mer
peptide (B2702.60-84) showed increased pathogenicity, indicating either a second arthritogenic
epitope or an immunomodulatory region within this
peptide. B2702.60-84 has been described to inhibit murine and human CD8 + cytotoxic T cells (CTL) and was even successfully used for the treatment of allograft rejection. In addition to pathogenicity we have investigated the immunomodulatory effect of
peptide B2702.60-84 in our rat model of experimental autoimmune
uveitis (EAU), induced with
retinal S-Antigen peptide PDSAg. We found that disease exacerbated following coimmunization of PDSAg with B2702.60-84. In vitro, the B27-peptide enhanced the proliferation of CD4+ T cell lines specific for
retinal autoantigen peptides during coincubation of B2702.60-84 with the respective
antigen. Oral tolerance induction, an effective mechanism to prevent
uveitis in Lewis rats, is abrogated by cofeeding
peptide B2702.60-84 with the
tolerogen PDSAg. In rat EAU, naturally occurring regulatory T cells and orally induced gamma deltaTCR+ suppressor cells are CD8+ which might be impeded by
peptide B2702.60-84. As a consequence of their abrogated suppressive capacity disease was exacerbated. We propose a similar role of
HLA-B27 in man: disturbing the mechanisms down-regulating self-responses might lead to
autoimmune diseases. This could explain the high association of
HLA-B27 with a variety of
autoimmune diseases targeting different organs or tissues.