T-CELL RECEPTOR (V-BETA) BIAS IN THE RESPONSE OF RHEUMATOID-ARTHRITISSYNOVIAL-FLUID T-CELLS TO CONNECTIVE-TISSUE ANTIGENS

T cell receptor (V beta) use in the response to type II collagen and c artilage proteoglycans was analysed in peripheral blood and synovial f luid T cells from RA patients. T cells from RA patients with an immune response to connective tissue antigens, and paired PB and SF samples were stimulated in vitro with type II collagen, high density aggrecan proteoglycans (PG), and the T cell mitogen concanavalin A. After short term culture, mRNA was extracted from cells and a reverse transcripti on-polymerase chain reaction was performed, using primers specific for eight TCR V beta determinants. Blood cells stimulated with ConA gener ated strong bands with virtually all the V beta primers tested, but th e TCR (V beta) expression by SF T cells stimulated with mitogen was bi ased, suggesting a selection process during joint infiltration. The V beta phenotypes of cells responding to PG was restricted in individual RA patients, but the pattern of V beta use in the the RA population w as not consistent. In contrast, the VD phenotypes of SF cells respondi ng to CII was highly biased in both individual patients and the RA pop ulation, with V beta 14, V beta 17, and V beta 8 phenotypes predominan t. We conclude that the T cell response to connective tissue antigens is restricted compared with mitogen stimulation, with the highest degr ee of TCR bias seen in the response of SF T cells to stimulation with type II collagen.