High frequencies of identical T cell clonotypes in synovial tissues of rheumatoid arthritis patients suggest the occurrence of common antigen-driven immune responses

Objective. To investigate T cell antigen receptor (TCR) clonotypes in rheumatoid arthritis (RA) lesions. Methods. Reverse transcriptase-polymerase chain reaction with TCR V-beta family-specific primers and subsequent single-strand conformation polymorphism (SSCP) analysis were performed. Direct nucleotide sequencing was also conducted. Results. A distinct clonal expansion of T cells was observed in the synovium. Furthermore, identical bands in samples of different areas of the same lesion were obtained by SSCP analysis. Nucleotide sequencing revealed that T cell clonotypes of identical mobility on SSCP analysis had the same nucleotide sequence and thus were identical clones. In 6 RA patients, 60-100 % of the expanded T cell clonotypes had identical migration patterns in 2 different samples, indicating that this percentage represents commonly existing T cell clonotypes in the affected joint. Furthermore, the J(beta)2.1 gene segment was used predominantly by the TCR V-beta clonotypes that commonly expanded in the different portions of the same joint. Conclusion. These results suggest that the immune response in RA is not random, but rather is driven by common stimuli.