Control of B cell lymphoma recognition via natural killer inhibitory receptors implies a role for human Vγ/Vδ2 T cells in tumor immunity

The V gamma 9/V delta 2 T cell receptor (TCR) is expressed by most human gamma delta T cells, We show here that cytotoxic T lymphocytes of the V gamma 9/V delta 2 subset, but not of the V delta 1 subset of human gamma delta T cells, express natural killer inhibitory receptors (KIR) with specificity for different HLA class I alleles that down-regulate TCR-mediated signaling in response to HLA class I-expressing B cell lymphomas. V gamma 9/V delta 2 T cell clones with a T helper cell phenotype lack KIR and produce lymphokines in response to most human B cell lymphomas, just as they do upon recognition of the HLA class I-deficient human Burkitt's lymphoma Daudi. Thus, human V gamma 9/V delta 2 T cells have an innate specificity for nonpolymorphic cell surface structures expressed by many lymphoma cells and their cytotoxic activity is controlled by KIR. These results imply a general role of human V gamma 9/V delta 2 T cells in the defense against hematopoietic tumors that is distinct from NK cells.