A novel T cell subset with trans-rearranged Vγ-Cβ TCRs shows Vβ expression is dispensable for lineage choice and MHC restriction.

αβ T cells, which express the α-β TCR heterodimer, express CD4 or CD8 coreceptors on cells that are MHC class I or MHC class II dependent. In contrast, γδ T cells do not express CD4 or CD8 and develop independently of MHC interaction. The factors that determine αβ and γδ lineage choice are not fully understood, and the determinants of MHC restriction of TCR specificity have been controversial. In this study we have identified a naturally occurring population of T cells expressing Vγ-Cβ receptor chains on the cell surface, the products of genomic trans-rearrangement between the Vγ2 gene and a variety of Dβ or Jβ genes, in place of an intact TCRβ-chain and in association with TCRα. Identification of this population allowed an analysis of the role of TCR variable regions in determining T cell lineage choice and MHC restriction. We found that Vγ2(+)Cβ(+) cells are positive for either CD4 or CD8 and are selected in an MHC class II- or MHC class I-dependent manner, respectively, thus following the differentiation pathway of αβ and not γδ cells and demonstrating that Vβ V region sequences are not required for selection of an MHC-restricted repertoire.