A possible role of two hydrophobic amino acids in antigen recognition by synovial T cells in rheumatoid arthritis

✍ Scribed by Toshiaki Maruyama; Ichiro Saito; Sachiko Miyake; Hiroshi Hashimoto; Kazuto Sato; Hideo Yagita; Ko Okumura; Nobuyuki Miyasaka

• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: English
• Weight: 783 KB
• Volume: 23
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.1830230903

✦ Synopsis

A possible role of two 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 blood (PB) T cells in RA. The TcR V gene repertoire of PB and SF T cells in RA and osteoarthritis was heterogeneous. In contrast,Vall in SF was expressed to a greater degree in three of five RA patients, and increased levels of Vfi6,1-3 were found in the SFof four of six RA, compared with paired PB. Of note,VP6, 1-3 was universally used in four RA patients with a disease duration of less than 10 years, irrespective of their HLA-DR types. This was in contrast to two other RA patients, suffering for more than 20 years,who showed different Va and Vfi usages. fi-chain sequence analysis in RA patients with a preference for Vfi6, 1-3 has shown that a few clones dominated in SF, whereas polyclonality was observed in PB. These findings suggest oligoclonal expansion of T cells in response to specific antigen(s) in the SF of these patients with RA of relatively short duration. Concomitant use of two hydrophobic amino acids, leucine and valine, in the Dp region was noticeable among the predominant SFclones.These two amino acids might directly contact a peptide specific for the induction of synovitis in RA patients. TcR-directed therapy may, therefore, be useful for the treatment of early RA synovitis.