CONTROL OF B-CELL LYMPHOMA RECOGNITION VIA NATURAL-KILLER INHIBITORY RECEPTORS IMPLIES A ROLE FOR HUMAN V-GAMMA V-DELTA-2 T-CELLS IN TUMOR-IMMUNITY/

The V gamma 9/V delta 2 T cell receptor (TCR) is expressed by most hum an gamma delta T cells, We show here that cytotoxic T lymphocytes of t he V gamma 9/V delta 2 subset, but not of the V delta 1 subset of huma n gamma delta T cells, express natural killer inhibitory receptors (KI R) with specificity for different HLA class I alleles that down-regula te 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 phe notype lack KIR and produce lymphokines in response to most human B ce ll lymphomas, just as they do upon recognition of the HLA class I-defi cient human Burkitt's lymphoma Daudi. Thus, human V gamma 9/V delta 2 T cells have an innate specificity for nonpolymorphic cell surface str uctures expressed by many lymphoma cells and their cytotoxic activity is controlled by KIR. These results imply a general role of human V ga mma 9/V delta 2 T cells in the defense against hematopoietic tumors th at is distinct from NK cells.