Differential expression of inhibitory or activating CD94/NKG2 subtypes on MART-1-reactive T cells in vitiligo versus melanoma: a case report.
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.
Pedersen
Lars Østergaard
LØ
Danish Cancer Society, Copenhagen, Denmark. becker-jc.derma@mail.uni-wuerzburg.de
Vetter
Claudia S
CS
Mingari
Maria C
MC
Andersen
Mads Hald
MH
thor Straten
Per
P
Bröcker
Eva-B
EB
Becker
Jürgen C
JC
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*
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