COLLAGEN-SPECIFIC CYTOTOXIC T-LYMPHOCYTE RESPONSES IN PATIENTS WITH ANKYLOSING-SPONDYLITIS AND REACTIVE ARTHRITIS

Both ankylosing spondylitis (AS) and reactive arthritis (ReA) are stro ngly associated with HLA-B27 although the mechanism for this associati on is still unknown. Here we examine the hypothesis that B27-restricte d, joint antigen-specific cytotoxic T lymphocytes (CTL) may be the dri ving force of AS and ReA. Type II and type XI procollagens (CII and CX I, respectively), expressed almost exclusively in the articular cartil age of the joints were chosen as the possible targets of autoimmune CT L. Type I procollagen (CI), expressed in many different tissues, was a lso included as control. Nineteen nonamer peptides bearing appropriate HLA-B27 binding motifs from human CI, CII and CXI were identified and synthesized. When analyzed for binding affinity to HLA-B27 in assembl y assays, four (two from CII, two from CXI) were found capable of bind ing to HLA-B27 with high affinity. These B27-binding collagen peptides were then used to stimulate peripheral blood lymphocytes from eight B 27-positive AS and three ReA patients for identification of possible B 27-restricted autoimmune CTL. HLA-B27-restricted CTL specific for one of the CII peptides, P109 were found in one of the ReA patients, but i n none of the others.