Clonally expanded CD4+CD28null T cells in rheumatoid arthritis use distinct combinations of T cell receptor BV and BJ elements

Clonally expanded, autoreactive CD4+CD28null cells can be found in the peripheral blood of patients with rheumatoid arthritis and have been shown to be associated with severeextra‐articular disease manifestations. We investigated the size of the CD4+CD28null compartment and the TCR β chain repertoire of expanded CD4+ clonotypes in 94 rheumatoid arthritis patients by complementarity‐determining region 3 (CDR3) length analysis (spectratyping) in the BV6 and BV14 TCR families, with primers specific for three arbitrarily chosen β chain joining elements (BJ1S2, BJ2S3 and BJ2S7). The spectratyping results showed a strong correlation of the size of the CD4+CD28null compartment with the detected number of BV14 clonotypes, whereas no association with BV6 oligoclonality was found. Only clones using the BV14–BJ1S2 and BV14–BJ2S3 combinations contributed to this correlation, however, whereas BV14–BJ2S7 clones did not. This preferential correlation implies a role for the TCR β chain in stimulating clonal outgrowth and argues against the previously suggested superantigenic stimulation of in‐vivo‐expanded clones. Instead, since no evidence for shared antigen specificity could be detected, clonal expansion of T cells in rheumatoid arthritis might be influenced by the BJ elements because of changes in the flexibility of the protein backbone of the β‐chain.