Sharing of T cell receptors in antigen-specific responses is driven by convergent recombination

Abstract

Public responses where identical T cell receptors (TCRs) are clonally dominant and shared between different individuals are a common characteristic of CD8(+) T cell-mediated immunity. Focusing on TCR sharing, we analyzed approximately 3,400 TCR beta chains (TCRbetas) from mouse CD8(+) T cells responding to the influenza A virus D(b)NP(366) and D(b)PA(224) epitopes. Both the "public" D(b)NP(366)-specific and "private" D(b)PA(224)-specific TCR repertoires contain a high proportion ( approximately 36%) of shared TCRbetas, although the numbers of mice sharing TCRbetas in each repertoire varies greatly. Sharing of both the TCRbeta amino acid and TCRbeta nucleotide sequence was negatively correlated with the prevalence of random nucleotide additions in the sequence. However, the extent of TCRbeta amino acid sequence sharing among mice was strongly correlated with the level of diversity in the encoding nucleotide sequences, suggesting that a key feature of public TCRs is that they can be made in a variety of ways. Using a computer simulation of random V(D)J recombination, we estimated the relative production frequencies and variety of production mechanisms for TCRbeta sequences and found strong correlations with the sharing of both TCRbeta amino acid sequences and TCRbeta nucleotide sequences. The overall conclusion is that "convergent recombination," rather than a bias in recombination or subsequent selection, provides the mechanistic basis for TCR sharing between individuals responding to identical peptide plus MHC class I glycoprotein complexes.