title: 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-2K(b) (K(b) )-associated peptides and critically required to induce full activation of H-2(k) monoclonal CD8(+) TLs expressing the cognate TCR-BM3.3. Here, we asked whether a pBM1/K(b) -specific TL subset could be detected within a polyclonal TL population rejecting allogeneic cells in vivo. We show that the proportion of pBM1/K(b) -binding CD8(+) TLs increased from <0.04% in naïve mice to 3% of activated CD44(+) CD8(+) TLs in H-2(k) mice rejecting K(b) -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 K(b) -reactive CD44(+) CD8(+) TLs not binding pBM1/K(b) displayed this CDR3β motif. We found that the recurrent CDR3β motif of pBM1/K(b) -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-K(b) TCR repertoire.
authors: Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, Marseille, France.
authors: Caroline
authors: C
authors: Scifo
authors: Laura
authors: L
authors: Mekaelian
authors: Elisaphane
authors: E
authors: Munyazesa
authors: Anne-Marie
authors: AM
authors: Schmitt-Verhulst
authors: Annick
authors: A
authors: Guimezanes