CD94/NKG2 inhibitory receptor complex modulates both anti-viral and anti-tumoral responses of polyclonal phosphoantigen-reactive V gamma 9V delta 2 T lymphocytes.
Viral, bacterial, protozoal, and cancer-associated Ags elicit strong responses in human gammadelta T lymphocytes. The majority of these cells in the peripheral blood express the Vgamma9Vdelta2-encoded TCR and recognize nonpeptidic phosphoantigens without an apparent MHC restriction. We have shown that Vgamma9Vdelta2 T cells express the inhibitory CD94/NKG2 receptor for HLA class I molecules. The anti-CD94 mAb inhibits 1) the Vgamma9Vdelta2 T cell proliferation in response mycobacterial phosphoantigens and 2) the HIV-induced Vgamma9Vdelta2 T cell expansion. Vgamma9Vdelta2 T cells stimulated with nonpeptidic 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 cytotoxic activity of Vgamma9Vdelta2 T cells. The Vgamma9Vdelta2 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.
Poccia
F
F
Department of Biology, University of Rome Tor Vergata, Italy. poccia@utovrm.it
Cipriani
B
B
Vendetti
S
S
Colizzi
V
V
Poquet
Y
Y
Battistini
L
L
López-Botet
M
M
Fournié
J J
JJ
Gougeon
M L
ML
D000942:Antigens, Bacterial / Q000276:immunology*; D015703:Antigens, CD / Q000096:biosynthesis / Q000502:physiology*; D000956:Antigens, Viral / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D016694:Gene Rearrangement, delta-Chain T-Cell Antigen Receptor; D005803:Genes, Immunoglobulin; D015497:HIV-1 / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism*; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000502:physiology*; D019907:Mycobacterium fortuitum / Q000276:immunology; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology* / Q000378:metabolism; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000502:physiology*; D011975:Receptors, Mitogen / Q000378:metabolism; D055607:Receptors, Natural Killer Cell; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014407:Tumor Cells, Cultured
D000942:Antigens, Bacterial; D015703:Antigens, CD; D000956:Antigens, Viral; D015395:Histocompatibility Antigens Class I; C527054:KLRC1 protein, human; C497869:KLRD1 protein, human; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011971:Receptors, Immunologic; D011975:Receptors, Mitogen; D055607:Receptors, Natural Killer Cell