Limited T-Cell Receptor β-Chain Heterogeneity Among Interleukin 2 Receptor-Positive Synovial T Cells Suggests a Role for Superantigen in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a disease affecting the synovial membranes of articulating joints that is thought to result from T-cell-mediated autoimmune phenomena. T cells responsible for the pathogenesis of RA are likely present in that fraction of synovial T cells that expresses the interleukin 2 receptor (IL-2R), one marker of T-cell activation. We report herein an analysis of T-cell receptor (TCR)β-chain gene expression by IL-2R-positive synovial T cells. These T cells were isolated from uncultured synovial tissue specimens by using IL-2R-specific monoclonal antibodies and magnetic beads, and TCR β-chain transcription was analyzed by PCR-catalyzed amplification using a panel of primers specific for the human TCR β-chain variable region (Vβ). Multiple Vβ gene families were found to be transcribed in these patient samples; however, three gene families, Vβ3, Vβ14, and Vβ17, were found in a majority of the five synovial samples analyzed, suggesting that T cells bearing these Vβ s had been selectively retained in the synovial microenvironment. In many instances, the Vβ3, Vβ14, or Vβ17 repertoires amplified from an individual patient were dominated by a single rearrangement, indicative of clonal expansion in the synovium and supportive of a role for these T cells in RA. Of note is a high sequence similarity between Vβ3, Vβ14, and Vβ17 polypeptides, particularly in the fourth complementarity-determining region (CDR). Given that binding sites for superantigens have been mapped to the CDR4s of TCR β chains, the synovial localization of T cells bearing Vβs with significant CDR4 homology indicates that Vβ-specific T-cell activation by superantigen may play a role in RA.