Genomically Imposed and Somatically Modified Human Thymocyte VβGene Repertoires

The effect of thymic selection on the expressed human T-cell antigen receptor β-chain variable region (Vβ) gene repertoire was examined by using a multiprobe RNase protection assay. The relative abundance of transcripts for 22 Vβgenes (encompassing 17 of the 20 human Vβgene subfamilies) within a thymus, and among 17 thymuses, was variable. On the basis of the presence of corresponding mRNAs, no genomic deletions were detected, but several coding regionpolymorphisms were identified. Analysis of mature T-cell subsets revealed the absence of complete "superantigen"-mediated Vβdeletions, suggesting that this phenomenon, in contrast to mouse, is uncommon or absent in humans. However, several Vβgenes were over- or underexpressed in one or both mature single-positive (CD4+8-or CD8+4-) thymocyte subsets compared to syngeneic total, mostly immature thymocytes. Whether these changes are induced by relatively weak superantigens or conventional antigens and whether the downshifts are caused by negative selection or lack of positive selection remains to be determined.