title: Control of self-reactive cytotoxic T lymphocytes expressing gamma delta T cell receptors by natural killer inhibitory receptors.
abstract: The majority of peripheral blood gamma delta T cells in human adults expresses T cell receptors (TCR) with identical V regions (V gamma 9 and V delta 2). These V gamma 9 V delta 2 T cells recognize the major histocompatibility complex (MHC) class I-deficient B cell line Daudi and broadly distributed nonpeptidic antigens present in bacteria and parasites. Here we show that unlike alpha beta or V gamma 9- gamma delta T cells, the majority of V gamma 9V delta 2 T cells harbor natural killer inhibitory receptors (KIR) (mainly CD94/NKG2A heterodimers), which are known to deliver inhibitory signals upon interaction with MHC class I molecules. Within V gamma 9V delta 2 T cells, KIR were mainly expressed by clones exhibiting a strong lytic activity against Daudi cells. In stark contrast, almost all V gamma 9V delta 2 T cell clones devoid of killing activity were KIR-, thus suggesting a coordinate acquisition of KIR and cytotoxic activity within V gamma 9V delta 2 T cells. In functional terms, KIR inhibited lysis of MHC class I-positive tumor B cell lines by V gamma 9V delta 2 cytotoxic T lymphocytes (CTL) and raised their threshold of activation by microbial antigens presented by MHC class I-positive cells. Furthermore, masking KIR or MHC class I molecules revealed a TCR-dependent recognition by V gamma 9V delta 2 CTL of ligands expressed by activated T lymphocytes, including the effector cells themselves. Taken together, these results suggest a general implication of V gamma 9V delta 2 T cells in immune response regulation and a central role of KIR in the control of self-reactive gamma delta CTL.
authors.affiliation: INSERM U463, Institute de Biologie, Nantes, France.
authors.forename: F
authors.initials: F
authors.lastname: Halary
authors.forename: M A
authors.initials: MA
authors.lastname: Peyrat
authors.forename: E
authors.initials: E
authors.lastname: Champagne
authors.forename: M
authors.initials: M
authors.lastname: Lopez-Botet
authors.forename: A
authors.initials: A
authors.lastname: Moretta
authors.forename: L
authors.initials: L
authors.lastname: Moretta
authors.forename: H
authors.initials: H
authors.lastname: Vié
authors.forename: J J
authors.initials: JJ
authors.lastname: Fournié
authors.forename: M
authors.initials: M
authors.lastname: Bonneville
mesh_terms: D000328:Adult; D002051:Burkitt Lymphoma; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006680:HLA Antigens / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000502:physiology; D006801:Humans; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D004915:Leukemia, Erythroblastic, Acute; D008213:Lymphocyte Activation / Q000187:drug effects; D018655:Lymphocyte Count; D009101:Multiple Myeloma; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis* / Q000502:physiology; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D054340:Receptors, KIR; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011971:Receptors, Immunologic; D054340:Receptors, KIR