THE V-BETA-17+ T-CELL REPERTOIRE - SKEWED J-BETA USAGE AFTER THYMIC SELECTION - DISSIMILAR CDR3S IN CD4+ VERSUS CD8+ CELLS

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 > 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 dear biases, probably due to idiosyncrasies of the recombination enzymes, and provide arguments that TCR and immunoglobulin CDR3s have distinct structures.