Different genes generate biased patterns of diversity in human T cells

The aim of this work was to assess whether each T-cell receptor () segment generates a random pattern of junctional diversity or if, alternatively, biased patterns of rearrangements limit the number of available specificities. Detailed molecular analysis of T-cell receptors expressed by lymphocytes was obtained by generating a large number of junctional regions sequences from , and variable genes. The > 800 sequences analyzed have allowed the characterization of the recombination frequencies of each germline-encoded , and segments, as well as of the magnitude of exonucleolytic nibbling and of the number of nucleotides inserted for each group of segments. The data obtained indicate that the extent of junctional diversity varies considerably depending on the gene implicated in the recombination event, due to the occurrence of skewed patterns of and region usage. Furthermore, our results show that “illegitimate” rearrangements occur with unexpectedly high incidence, specifically at the level of to joining. These findings provide additional information for a more accurate estimation of the size of the repertoire and for understanding the well-established biased pattern of expression in humans.