The CD8؉ TCR repertoires specific for many immunogenic epitopes of CMV and EBV are dominated by a few TCR clonotypes and involve public TCRs that are shared between many MHC-matched individuals. In previous studies, we demonstrated that the observed sharing of epitope-specific TCR␤ chains between individuals is strongly associated with TCR␤ production frequency, and that a process of convergent recombination facilitates the more efficient production of some TCR␤ sequences. In this study, we analyzed a total of 2836 TCR␤ sequences from 23 CMV-infected and 10 EBV-infected individuals to investigate the factors that influence the sharing of TCR␤ sequences in the CD8 ؉ T cell responses to two immunodominant HLA-A*0201-restricted epitopes from these viruses. The most shared TCR␤ amino acid sequences were found to have two features that indicate efficient TCR␤ production, as follows: 1) they required fewer nucleotide additions, and 2) they were encoded by a greater variety of nucleotide sequences. We used simulations of random V(D)J recombination to demonstrate that the in silico TCR␤ production frequency was predictive of the extent to which both TCR␤ nucleotide and amino acid sequences were shared in vivo. These results suggest that TCR␤ production frequency plays an important role in the interindividual sharing of TCR␤ sequences within CD8 ؉ T cell responses specific for CMV and EBV.

In some epitope-specific responses, T cells bearing identical TCRs occur in many MHC-matched individuals. The sharing of public TCRs is unexpected, given the enormous potential diversity of the TCR repertoire. We have previously studied the sharing of TCR β-chains in the CD8+ T cell responses to two influenza epitopes in mice. Analysis of these TCRβ repertoires suggests that, even with unbiased V(D)J recombination mechanisms, some TCRβs can be produced more frequently than others, by a process of convergent recombination. The TCRβ production frequency was shown to be a good predictor of the observed sharing of epitope-specific TCRβs between mice. However, this study was limited to immune responses in an inbred population. In this study, we investigated TCRβ sharing in CD8+ T cell responses specific for the immunodominant Mamu-A*01-restricted Tat-SL8/TL8 and Gag-CM9 epitopes of SIV in rhesus macaques. Multiple data sets were used, comprising a total of ∼6000 TCRβs sampled from 20 macaques. We observed a spectrum in the number of macaques sharing epitope-specific TCRβs in this outbred population. This spectrum of TCRβ sharing was negatively correlated with the minimum number of nucleotide additions required to produce the sequences and strongly positively correlated with the number of observed nucleotide sequences encoding the amino acid sequences. We also found that TCRβ sharing was correlated with the number of times, and the variety of different ways, the sequences were produced in silico via random gene recombination. Thus, convergent recombination is a major determinant of the extent of TCRβ sharing.

Shigella flexneri, which causes shigellosis in humans, evolved from Escherichia coli. The sequencing of Shigella genomes has revealed that a large number of insertion sequence (IS) elements (over 200 elements) reside in the genome. Although the presence of these elements has been noted previously and summarized, more detailed analyses are required to understand their evolutionary significance. Here, the genome of S. flexneri strain 2457T is used to investigate the spatial distribution of IS copies around the chromosome and the location of elements with respect to genes. It is found that most IS isoforms occur essentially randomly around the genome. Two exceptions are IS91 and IS911, which appear to cluster due to local hopping. The location of IS elements with respect to genes is biased, however, revealing the action of natural selection. The non-coding regions of the genome (no more than 21%) carry disproportionally more IS elements (at least 28%) than the coding regions, implying that selection acts against insertion into genes. Of the genes disrupted by ISs, those involved in signal transduction, intracellular trafficking, and cell motility are most commonly targeted, suggesting selection against genes in these categories.