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Keywords:

  • Natural killer receptor;
  • γδ T lymphocyte;
  • B cell lymphoma

Abstract

The Vγ9/Vδ2 T cell receptor (TCR) is expressed by most human γδ T cells. We show here that cytotoxic T lymphocytes of the Vγ9/Vδ2 subset, but not of the Vδ1 subset of human γδ 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. Vγ9/Vδ2 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 l-deficient human Burkitt's lymphoma Daudi. Thus, human Vγ9/Vδ2 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 Vγ9/Vδ2 T cells in the defense against hematopoietic tumors that is distinct from NK cells.