title: Up-regulation of cytolytic functions of human Vδ2-γ T lymphocytes through engagement of ILT2 expressed by tumor target cells.
abstract: In humans, the majority of peripheral blood γδ T cells expresses Vγ9Vδ2 T-cell receptors (TCR) and recognize nonpeptidic phosphorylated antigens. In contrast, most tissue-derived γδ T cells, which are located mainly in spleen and epithelia, preferentially use Vδ1 or Vδ3 chains paired with diverse Vγ chains to form their TCR. Our knowledge about the antigenic specificity and costimulation requirements of human Vδ2(-) γδ T cells remains limited. In an attempt to address this important issue, we characterized the specificity of a monoclonal antibody (mAb 256), screened for its ability to specifically inhibit cytolytic responses of several human Vδ2(-) γδ T-cell clones against transformed B cells. We show that mAb 256 does not target a TCR ligand but blocks key interactions between non-TCR molecules on effector γδ T cells and ILT2 molecule, expressed by tumor targets. In line with the previously reported specificity of this NK receptor for classic and nonclassic major histocompatibility complex (MHC) class I molecules, blockade of MHC class I/ILT2 interactions using MHC class I- or ILT2-specific mAbs and ILT2-Fc molecules inhibited tumor-induced activation of Vγ8Vδ3 T-cell clones. Therefore, this study describes a new cytotoxic T lymphocyte activation pathway involving MHC class I engagement on γδ T cells.
authors.affiliation: Inserm Unité Mixte de Recherche 892, Centre de Recherche en Cancérologie Nantes-Angers, Institut de Recherche Thérapeutique Université de Nantes, Nantes, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Harly
authors.forename: Marie-Alix
authors.initials: MA
authors.lastname: Peyrat
authors.forename: Sonia
authors.initials: S
authors.lastname: Netzer
authors.forename: Julie
authors.initials: J
authors.lastname: Déchanet-Merville
authors.forename: Marc
authors.initials: M
authors.lastname: Bonneville
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Scotet
mesh_terms: D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D008213:Lymphocyte Activation / Q000276:immunology*; D018613:Microscopy, Confocal; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology / Q000378:metabolism; D011971:Receptors, Immunologic / Q000276:immunology* / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; D015395:Histocompatibility Antigens Class I; C105299:LILRB1 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011971:Receptors, Immunologic