Oligoclonal T Cells in Rheumatoid Arthritis: Identification Strategy and Molecular Characterization of a Clonal T‐Cell Receptor

Abstract

Immunodominant antigens in rheumatoid arthritis (RA) should induce an expansion of T cells bearing a corresponding T‐cell receptor (TCR). We therefore analysed the TCR repertoire at the site of inflammation using two fundamentally different strategies. The total TCR repertoire was examined by generating‘representative’T‐cell clone panels, which were subsequently tested for clonality by restriction mapping of the TCRβ gene locus. No clonality was detected in large T‐cell clone panels generated with cells from three patients. However, when we selectively analysed the TCR repertoire of in vivo pre‐activated, interleukin‐2 (IL‐2)‐responsive T cells, significant T‐cell/TCR clonality was found in 2 out or4 patients. The clonal T cells represented a minority of the total T‐cell population with an estimated frequency of 1 in 300 to 1 in 1000 cells. Molecular characterization of a clonal TCR and the use of a specific TCR Vβ MoAb ruled out an over representation of T cells bearing the same Vβlelement in the total T‐cell population, rendering the involvement of superantigens in the induction of T‐cell clonality in this case unlikely.