Selection of T-cell receptors with a recurrent CDR3β peptide-contact motif within the repertoire of alloreactive CD8+ T cells

Abstract

Peptide/MHC complexes recognized by alloreactive T lymphocytes (TLs) have been identified, but their contribution to in vivo allo-rejection is not known. We previously characterized the peptide pBM1, highly represented among endogenous H-2Kb (Kb)-associated peptides and critically required to induce full activation of H-2k monoclonal CD8+ TLs expressing the cognate TCR-BM3.3. Here, we asked whether a pBM1/Kb-specific TL subset could be detected within a polyclonal TL population rejecting allogeneic cells in vivo. We show that the proportion of pBM1/Kb-binding CD8+ TLs increased from <0.04% in naïve mice to 3% of activated CD44+ CD8+ TLs in H-2k mice rejecting Kb-expressing cells. Among these, TCR-Vβ2 usage was greatly enriched, and 75% of them shared a TCR-Vβ2 CDR3β motif with the prototype TCR-BM3.3. Fewer than 5% of Kb-reactive CD44+ CD8+ TLs not binding pBM1/Kb displayed this CDR3β motif. We found that the recurrent CDR3β motif of pBM1/Kb-binding TLs was assembled from distinct V/D/J recombination events, suggesting that it is recruited upon immunization for its optimal TCR-peptide/MHC fit. Thus, a CDR3β motif generated by a process akin to "convergent recombination" accounts for a sizable fraction of the alloreactive anti-Kb TCR repertoire. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.