Analysis of T cell antigen receptor (TCR) expression by human peripheral blood CD4⁻8⁻ αβ T cells demonstrates preferential use of several Vβ genes and an invariant TCR α chain

CD4⁻CD8⁻ (double negative [DN]) α/β T cells are a largely uncharacterized subpopulation of unknown function. To investigate whether these cells are selected to recognize particular antigens or antigen-presenting molecules, DN α/β T ceils were purified from the peripheral blood of five normal donors and their T cell receptor (TCR) α and β chains were examined. Random cloning of TCR α chains by single-sided polymerase chain reaction (PCR) amplification identified an invariant rearrangement between Vα24 and JαQ, with no N region diversity, which was expressed preferentially by DN α/β T cells from all donors. Random cloning also identified a precise Vα7.2-Jα(IGRJa14) rearrangement, with two variable amino acids encoded in the V-J junction, which was enriched in the DN α/β T cell preparations from some, but not all, donors. Analysis of TCR β chains by quantitative PCR amplification demonstrated that the expression of four Vβ gene families, Vβ2, 8, 11, and 13, was markedly increased in these DN α/β T cell preparations. The expression of particular TCRs by DN α/β T cells from multiple donors indicates that these ceils, or at least a subpopulation of cells with this phenotype, recognize a limited spectrum of antigens and suggests that they may use nonpolymorphic antigen-presenting molecules.