The predominant subpopulation of gamma delta T cells in human peripheral blood expresses TCR V region genes V gamma 2 paired with V delta 2. Previous studies have shown that these V gamma 2V delta 2+ 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 gamma delta T cell proliferation via TCR-dependent recognition. Here we report that transfection of TCR- Jurkat T cells with cDNA constructs encoding a V gamma 2V delta 2 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 gamma delta TCR in V gamma 2V delta 2 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 gamma delta T cells.

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