BIASED T-CELL RECEPTOR-V GENE USAGE IN RHEUMATOID-ARTHRITIS - OLIGOCLONAL EXPANSION OF T-CELLS EXPRESSING V-ALPHA-2 GENES IN SYNOVIAL-FLUID BUT NOT IN PERIPHERAL-BLOOD

Objective. To analyze the T cell receptor (TCR) variable (V) region gene usage in the rheumatoid joint. Methods. Monoclonal antibodies (MAb) were used to determine the prevalence of selected V elements on T cells in synovial fluid (SF) from rheumatoid arthritis (RA) patients and in peripheral blood (PB) from RA patients and normal controls. V(alpha)2-positive PB and SF T cells from 1 patient were cloned by immediated limiting-dilution and analyzed by restriction mapping. Results. In 9 of 14 RA patients, SF was enriched in at least 1 of the selected V elements, compared with PB. TCR genes of the V(alpha) 2 family were the most frequently overrepresented in the SF (4 patients). The expanded V(alpha) 2-positive cells were oligoclonal in SF but heterogeneic in PB. Conclusion. Our data showing biased and clonally restricted TCR elements in the rheumatoid joint indicate major histocompatibility complex-restricted antigen recognition, rather than a ''superantigen,'' in the pathogenesis of RA.