Human T cell receptor-mediated recognition of HLA-E.
The HLA-E class Ib molecule presents hydrophobic peptides derived from the leader sequences of other class I molecules, constituting the ligands for CD94/NKG2 lectin-like receptors. Along the course of our studies on human CD94+ T cells, we characterized an alpha beta CD8+CD94/NKG2C+ CTL clone (K14). In cytolytic assays against the murine TAP-deficient RMA-S cells transfected with human beta2 microglobulin and HLA-E (RMA-S/HLA-E), loaded with different synthetic peptides, K14 displayed a pattern of specific recognition distinct to that observed in CD94/NKG2C+ NK clones tested in parallel. RMA-S/HLA-E cells loaded with some but not all HLA class I leader sequence peptides were efficiently recognized by K14 but not by CD94/NKG2C clones, andvice versa. Remarkably, K14 also reacted with HLA-E loaded with a peptide derived from the BZLF-1 Epstein-Barr virus protein. Anti-CD94 mAb did not prevent K14 cytotoxicity against RMA-S/HLA-E cells, whereas incubation with anti-clonotypic mAb specific for the K14 TCR markedly inhibited lysis. Soluble HLA-E tetramers refolded with different peptides (i.e. VMAPRTVLL, VMAPRTLIL, VMAPRTLFL) specifically stained K14 cells. HLA-E tetramer binding was minimally reduced by pretreatment with anti-CD94 mAb alone, but was completely prevented in combination with anti-clonotypic mAb. Altogether, the data unequivocally imply the generation of human T cells potentially recognizing through the alpha beta TCR HLA-E molecules that bind to class I- and virus-derived peptides.
García
Pilar
P
DCEXS (Inmunología), Universitat Pompeu Fabra, Barcelona, Spain.
Llano
Manuel
M
de Heredia
Agustín B
AB
Willberg
Christian B
CB
Caparrós
Esther
E
Aparicio
Pedro
P
Braud
Véronique M
VM
López-Botet
Miguel
M
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D017951:Antigen Presentation; D015703:Antigens, CD / Q000276:immunology; D000956:Antigens, Viral / Q000737:chemistry / Q000276:immunology*; D001704:Biopolymers; D002999:Clone Cells / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000276:immunology*; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology*; D015234:HLA-A Antigens / Q000737:chemistry / Q000276:immunology; D015235:HLA-B Antigens / Q000737:chemistry / Q000276:immunology; D015236:HLA-C Antigens / Q000737:chemistry / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D051920:NK Cell Lectin-Like Receptor Subfamily D; D010446:Peptide Fragments / Q000276:immunology*; D021382:Protein Sorting Signals; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D015534:Trans-Activators / Q000737:chemistry / Q000276:immunology*; D014162:Transfection; D014764:Viral Proteins; D001613:beta 2-Microglobulin / Q000235:genetics; D000097625:HLA-E Antigens
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000956:Antigens, Viral; D001704:Biopolymers; D004268:DNA-Binding Proteins; D006680:HLA Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D015395:Histocompatibility Antigens Class I; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D051920:NK Cell Lectin-Like Receptor Subfamily D; D010446:Peptide Fragments; D021382:Protein Sorting Signals; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014764:Viral Proteins; D001613:beta 2-Microglobulin; D000097625:HLA-E Antigens; C063676:BZLF1 protein, Herpesvirus 4, Human; C497869:KLRD1 protein, human; C497870:Klrd1 protein, mouse; C489516:Tap2 protein, mouse; C071692:TAP2 protein, human