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, V alpha 11 in SF was expressed to a greater degree in three of five RA patients, and increased levels of V beta 6, 1-3 were found in the SF of four of six RA, compared with paired PB. Of note, V beta 6, 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 V alpha and V beta usages. beta-chain sequence analysis in RA patients with a preference for V beta 6, 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 D beta region was noticeable among the predominant SF clones. 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.
Maruyama
T
T
First Department of Internal Medicine, Tokyo Medical and Dental University, Japan.
Saito
I
I
Miyake
S
S
Hashimoto
H
H
Sato
K
K
Yagita
H
H
Okumura
K
K
Miyasaka
N
N
D000368:Aged; D000595:Amino Acid Sequence; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001483:Base Sequence; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007930:Leucine / Q000502:physiology*; D008875:Middle Aged; D008969:Molecular Sequence Data; D010003:Osteoarthritis / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D013582:Synovial Fluid / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014633:Valine / Q000502:physiology*
D006684:HLA-DR Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D007930:Leucine; D014633:Valine