title: The CD94/NKG2C killer lectin-like receptor constitutes an alternative activation pathway for a subset of CD8+ T cells.
abstract: The CD94/NKG2C killer lectin-like receptor (KLR) specific for HLA-E is coupled to the KARAP/DAP12 adapter in a subset of NK cells, triggering their effector functions. We have studied the distribution and function of this KLR in T lymphocytes. Like other NK cell receptors (NKR), CD94/NKG2C was predominantly expressed by a CD8(+) T cell subset, though TCRgammadelta(+) NKG2C(+) and rare CD4(+) NKG2C(+) cells were also detected in some individuals. Coculture with the 721.221 HLA class I-deficient lymphoma cell line transfected with HLA-E (.221-AEH) induced IL-2Ralpha expression in CD94/NKG2C+ NK cells and a minor subset of CD94/NKG2C(+) T cells, promoting their proliferation; moreover, a similar response was triggered upon selective engagement of CD94/NKG2C with a specific mAb. CD8(+) TCRalphabeta CD94/NKG2C(+) T cell clones, that displayed different combinations of KIR and CD85j receptors, expressed KARAP/DAP12 which was co-precipitated by an anti-CD94 mAb. Specific engagement of the KLR triggered cytotoxicity and cytokine production in CD94/NKG2C(+) T cell clones, inducing as well IL-2Ralpha expression and a proliferative response. Altogether these results support that CD94/NKG2C may constitute an alternative T cell activation pathway capable of driving the expansion and triggering the effector functions of a CTL subset.
authors.affiliation: Molecular Immunopathology Unit, Universitat Pompeu Fabra (DCEXS), Barcelona, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Gumá
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Busch
authors.forename: Laura I
authors.initials: LI
authors.lastname: Salazar-Fontana
authors.forename: Beatriz
authors.initials: B
authors.lastname: Bellosillo
authors.forename: Carles
authors.initials: C
authors.lastname: Morte
authors.forename: Pilar
authors.initials: P
authors.lastname: García
authors.forename: Miguel
authors.initials: M
authors.lastname: López-Botet
mesh_terms: D015703:Antigens, CD / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D005434:Flow Cytometry; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D037181:Lectins, C-Type / Q000502:physiology*; D008213:Lymphocyte Activation / Q000276:immunology*; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011971:Receptors, Immunologic / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000276:immunology; D055607:Receptors, Natural Killer Cell; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D014162:Transfection; D000097625:HLA-E Antigens
chemical_list: D015703:Antigens, CD; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D037181:Lectins, C-Type; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D055607:Receptors, Natural Killer Cell; D000097625:HLA-E Antigens; C527059:KLRC2 protein, human; C497869:KLRD1 protein, human