The V$_\beta$ 17$^+$ T cell repertoire: skewed J$\beta$ usage after thymic selection; dissimilar CDR3s in CD4$^+$ versus CD8$^+$ cells.
Résumé
To ascertain how the actual repertoire of T cell receptors (TCRs) deviates from the theoretical, we have generated a large number of junctional region sequences from TCRs carrying the V$_\beta$17 variable region. The greater than 600 sequences analyzed represent transcripts from nine different cell populations, permitting several comparisons: transcripts from an expressed vs. a non-expressed V$_\beta$17 allele, those from E$^+$ vs. E$^-$ mice, transcripts from immature vs. mature thymocytes, those from thymic vs. peripheral T cells, and those from CD4$^+$ vs. CD8$^+$ cells. These comparisons have allowed us to distinguish between the influence of molecular events involved in TCR gene rearrangement and that of various selection events that shape the T cell repertoire. Our most striking findings are: (a) that J$\beta$ usage is markedly skewed, partly due to recombination mechanics and partly due to selection forces: in particular, those mediated by the class II E molecule in the thymus; and (b) that TCRs on CD4$^+$ and CD8$^+$ cells show intriguing dissimilarities. In addition, we present evidence that N nucleotide additions occur with clear biases, probably due to idiosyncrasies of the recombination enzymes, and provide arguments that TCR and immunoglobulin CDR3s have distinct structures.
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