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.