Individual Vγ2-Jγ1.2+ T cells respond to both isopentenyl pyrophosphate and Daudi cell stimulation:: generating tumor effectors with low molecular weight phosphoantigens

Human V gamma 2V delta 2 T cells exhibit T cell receptor-dependent, MHC-unrestricted recognition of antigen and play important roles in tumor and pathogen immunity. To characterize antigen recognition by the V gamma 2V delta 2 TCR, we used the combined approach of spectratyping and CDR3 sequence analysis that measures changes in the TCR repertoire before and after stimulation with a phosphoantigen (isopentenyl pyrophosphate) or an irradiated tumor cell line (Daudi B lymphoma). Here we describe common V gamma 2 chains that are substantially involved in the response to both phosphoantigens and tumor cells. The recognition properties of common V gamma 2 chains explains the observation that V gamma 2V delta 2 T cells expanded by phosphoantigen stimulation specifically recognize and kill some but not all tumor cell lines. Our studies further justify efforts to stimulate tumor immunity by administering low molecular weight phosphoantigens and boosting the frequency and tumor effector functions of circulating V gamma 2V delta 2 T cells.