Vγ2Vδ2 TCR-dependent recognition of non-peptide antigens and Daudi cells analyzed by TCR gene transfer

The predominant subpopulation of γδ T cells in human peripheral blood expresses TCR V region genes Vγ2 paired with Vδ2. Previous studies have shown that these Vγ2Vδ2 T cells proliferate in response to Daudi Burkitt lymphoma cells, synthetic alkyl phosphate molecules including monoethylphosphate (MEP), and an Ag chemically similar to MEP purified from mycobacterial extracts of several species including Mycobacterium tuberculosis. This proliferation is polyclonal and determined by the TCR V gene. However, because these alkyl phosphate molecules are so distinct from conventional peptides and superantigens, we questioned whether these substances induce γδ T cell proliferation via TCR-dependent recognition. Here we report that transfection of TCR^- Jurkat T cells with cDNA constructs encoding a Vγ2Vδ2 TCR enabled the transfectants to produce IL-2 in response to Daudi cells, mycobacterial extract, and MEP. The responses were dose dependent and Ag specific. These results demonstrate an essential role for the γδ TCR in Vγ2Vδ2 T cell mediated recognition of non-peptide Ags by human T cells and suggest a structural similarity or cross-reactivity between cellular and microbial Ags recognized by these γδ T cells.