HETEROGENEITY OF THE TCR REPERTOIRE IN SYNOVIAL-FLUID T-LYMPHOCYTES RESPONDING TO BCG IN A PATIENT WITH EARLY RHEUMATOID-ARTHRITIS

T lymphocytes have been implicated in the pathogenesis of rheumatoid a rthritis. Interestingly, many of the activated T cells isolated from t he synovial fluid of individuals with rheumatoid arthritis react with antigens from Mycobacterium tuberculosis or BCG. This response is seen to a much lesser extent in the peripheral blood of these patients. To investigate the nature of the T-cell response to BCG in RA, we isolat ed T cells from the synovial fluid of a patient with early-stage rheum atoid arthritis, stimulated them with BCG and cloned by limiting dilut ion. Staining with monoclonal antibodies specific for different Vbeta gene families revealed a statistically significant greater proportion of synovial-derived T-cell clones expressing the Vbeta8 gene family pr oduct compared with peripheral blood clones. While the antigen specifi city of some of the clones could not be determined, several of the clo nes displayed distinct antigen reactivities. Sequencing the TCR beta c hain genes of these T cells suggested that although the Vbeta8 gene pr oducts appeared to be over-represented in these BCG-specific clones, e ach clone utilized distinct Jbeta gene segments and used N segment add ition to different extents. In addition, no common motifs were identif ied in the beta chain CDR3s of the clones sequenced. Analysis of bulk cultured BCG-specific SF T cells and unstimulated peripheral blood T c ells for Vbeta8 gene expression also revealed a large amount of divers ity within the CDR3 region. Thus, the T-lymphocyte response to BCG in this patient with early rheumatoid arthritis appears to be quite heter ogeneous.