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

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 approximate to 3,400 TCR beta chains (TCR beta s) from mouse CD8(+) T cells responding to the influenza A virus (DNP366)-N-b and D(b)PA(224) epitopes. Both the public (DNP366)-N-b-Specific and private D(b)PA(224)-specific TCR repertoires contain a high proportion (approximate to 36%) of shared TCR beta s, although the numbers of mice sharing TCR beta s in each repertoire varies greatly. Sharing of both the TCR beta amino acid and TCR beta nucleoticle sequence was negatively correlated with the prevalence of random nucleoticle additions in the sequence. However, the extent of TCR beta 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 TCR beta sequences and found strong correlations with the sharing of both TCR beta amino acid sequences and TCR beta nucleoticle 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.