CD94 NKG2 INHIBITORY RECEPTOR COMPLEX MODULATES BOTH ANTIVIRAL AND ANTI-TUMORAL RESPONSES OF POLYCLONAL PHOSPHOANTIGEN-REACTIVE V-GAMMA-9V-DELTA-2 T-LYMPHOCYTES/

Viral, bacterial, protozoal, and cancer-associated Ags elicit strong r esponses in human gamma delta T lymphocytes. The majority of these cel ls in the peripheral blood express the V gamma 9V delta 2-encoded TCR and recognize nonpeptidic phosphoantigens without an apparent MHC rest riction. We have shown that V gamma 9V delta 2 T cells express the inh ibitory CD94/NKG2 receptor for HLA class I molecules. The anti-CD94 mA b inhibits 1) the V gamma 9V delta 2 T cell proliferation in response mycobacterial phosphoantigens and 2) the HIV-induced V gamma 9V delta 2 T cell expansion. V gamma 9V delta 2 T cells stimulated with nonpept idic mycobacterial antigens produce IFN-gamma and TNF-alpha. Signaling through the CD94/NKG2 receptor interferes with the synthesis of these cytokines. The CD94/HLA class I interaction is also involved in the c ytotoxic activity of V gamma 9V delta 2 T cells. The V gamma 9V delta 2 T cell regulation through the CD94 receptor may be important for the potentially dual function in innate immunity, i.e., 1) NK-like and 2) TCR ligand-induced cytolytic activities.