Selection and long-term persistence of reactive CTL clones during an EBV chronic response are determined by avidity, CD8 variable contribution compensating for differences in TCR affinities

Recent studies have suggested that the diversity of TCR repertoire after pr imary immunization is conserved in memory T cells and that a progressive na rrowing of this repertoire may take place during recall infections. It now remains to be investigated which parameters determine the repertoire of the memory response and possibly restrict its diversity after subsequent antig enic challenges, To address this question, we took advantage of a panel of CD8(+) T cell clones from the joint of a rheumatoid arthritis patient and s elected for their reactivity against a single MHC/peptide complex. Characte rization of both TCR chains documented a great diversity among those clones and the persistence of clonotypes over a 2-yr period. Strikingly, despite the observed repertoire heterogeneity, all clones displayed a narrow range of MHC/peptide density requirements in cytotoxicity assays (ED50 between 9 and 36 nM), TCR affinities were then indirectly estimated by blocking CD8 i nteraction with an anti-CDS mAb, We found a wide range of TCR affinities am ong the different clonotypes that segregated with V beta usage. We thus pro pose that during an in vivo chronic response, a narrow range of avidity of the TCR-CD8 complex conditions long-term clonotype persistence, and that th e level of CD8 contribution is adjusted to keep clonotypes with variable TC R affinities within this avidity window.