A POSSIBLE ROLE OF 2 HYDROPHOBIC AMINO-ACIDS IN ANTIGEN RECOGNITION BY SYNOVIAL T-CELLS IN RHEUMATOID-ARTHRITIS

Synovial T cells play a crucial role in the pathogenesis of rheumatoid arthritis (RA) synovitis. We have quantitatively analyzed the T cell receptor (TcR) variable (V) region gene repertoire of freshly isolated synovial fluid (SF) T cells, comparing it with that of peripheral blo od (PB) T cells in RA. The TcR V gene repertoire of PB and SF T cells in RA and osteoarthritis was heterogeneous. In contrast, Valpha11 in S F was expressed to a greater degree in three of five RA patients, and increased levels of Vbeta6, 1-3 were found in the SF of four of six RA , compared with paired PB. Of note, Vbeta6, 1-3 was universally used i n four RA patients with a disease duration of less than 10 years, irre spective of their HLA-DR types. This was in contrast to two other RA p atients, suffering for more than 20 years, who showed different Valpha and Vbeta usages. Beta-chain sequence analysis in RA patients with a preference for Vbeta6, 1-3 has shown that a few clones dominated in SF , whereas polyclonality was observed in PB. These findings suggest oli goclonal expansion of T cells in response to specific antigen(s) in th e SF of these patients with RA of relatively short duration. Concomita nt use of two hydrophobic amino acids, leucine and valine, in the Dbet a region was noticeable among the predominant SF clones. These two ami no acids might directly contact a peptide specific for the induction o f synovitis in RA patients. TcR-directed therapy may, therefore, be us eful for the treatment of early RA synovitis.