title: Differential expression of inhibitory or activating CD94/NKG2 subtypes on MART-1-reactive T cells in vitiligo versus melanoma: a case report.
abstract: Selection and activation of T cells is tightly regulated by both antigen-specific receptors and co-receptors to ensure that responses to self antigens are largely avoided. By T cell receptor clonotypic mapping and staining with tetrameric HLA-peptide complexes, we demonstrate the presence of melanocyte differentiation antigen MART-1 specific T cells in the areas of destruction of both neoplastic and normal melanocytic cells in a case of a primary melanoma and its associated hypopigmentation. These self reactive T cells expressed CD94/NKG2 major histocompatibility complex class I specific C-type lectin-like receptors. This family of receptors includes both activating and inhibitory isoforms. Thus, we performed a detailed analysis that revealed the exclusive presence of inhibitory NKG2-A/B receptors in the vitiligo-like leukoderma, whereas both the inhibitory receptors and the activating NKG2-C/E isoforms were present within the tumor. Our data suggest the differential expression of killer inhibitory receptors as a possible mechanism to regulate T cell responses to self antigens.
authors.affiliation: Danish Cancer Society, Copenhagen, Denmark. becker-jc.derma@mail.uni-wuerzburg.de
authors.forename: Lars Østergaard
authors.initials: LØ
authors.lastname: Pedersen
authors.forename: Claudia S
authors.initials: CS
authors.lastname: Vetter
authors.forename: Maria C
authors.initials: MC
authors.lastname: Mingari
authors.forename: Mads Hald
authors.initials: MH
authors.lastname: Andersen
authors.forename: Per
authors.initials: P
authors.lastname: thor Straten
authors.forename: Eva-B
authors.initials: EB
authors.lastname: Bröcker
authors.forename: Jürgen C
authors.initials: JC
authors.lastname: Becker
mesh_terms: D015703:Antigens, CD / Q000235:genetics; D000951:Antigens, Neoplasm; D015551:Autoimmunity / Q000276:immunology; D002999:Clone Cells; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007150:Immunohistochemistry; D037181:Lectins, C-Type; D058965:MART-1 Antigen; D008545:Melanoma / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D009363:Neoplasm Proteins / Q000032:analysis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D011971:Receptors, Immunologic / Q000235:genetics; D055607:Receptors, Natural Killer Cell; D012878:Skin Neoplasms / Q000276:immunology*; D013601:T-Lymphocytes / Q000737:chemistry / Q000166:cytology / Q000276:immunology*; D014820:Vitiligo / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; C527054:KLRC1 protein, human; C527059:KLRC2 protein, human; C497869:KLRD1 protein, human; D037181:Lectins, C-Type; D058965:MART-1 Antigen; C548667:MLANA protein, human; D008562:Membrane Glycoproteins; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D009363:Neoplasm Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell