Few V gene segments dominate the T cell receptor beta-chain repertoire of the human thymus.
We undertook a large sample census of the TCR-beta repertoire from a single human thymus (300 clones from an unamplified cDNA library), to establish the statistics of the rearranged V, D, J, and C gene segments. The assortments of all germ-line segments are subject to significant biases and thus critically reduce the effective germ-line contribution to beta-chain diversity. Thirty-two V genes characterize the whole sample, but surprisingly as few as seven genes from different families encompass half of the beta-chain repertoire. Furthermore, a Spearman rank order correlation test of the thymic V beta frequencies with those inferred in other studies using RNase protection assays shows a statistically significant similarity. Thus, in the establishment of thymic V beta frequencies in man, rearrangement preferences intrinsic to the progenitors of TCR-beta expressing cells override HLA- and Ag-dependent biasing factors. By implication, a large enough pool of direct progenitor cells (maybe as high as thousands) must exist to secure V beta frequencies against large random fluctuations. Uncorrelated with the V gene bias, the representation of D beta and J beta segments is also far from even. Notably, D beta 1 and J beta 2.1 and 1.2 predominate. Using the above mentioned rank order statistic, we also find that unlike V genes, the bias in the J segment usage carries over into the frequencies of peripheral T lymphocyte populations.
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Unité d'Immunogénétique, Institut National de la Santé et de la Recherche Médicale, Institut Pasteur, Paris, France.
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D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D002675:Child, Preschool; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000235:genetics*; D013601:T-Lymphocytes / Q000737:chemistry; D013950:Thymus Gland / Q000737:chemistry*
D016693:Receptors, Antigen, T-Cell, alpha-beta