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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.

Original publication




Journal article


Eur J Immunol

Publication Date





936 - 944


ATP Binding Cassette Transporter, Subfamily B, Member 3, ATP-Binding Cassette Transporters, Animals, Antibodies, Monoclonal, Antigen Presentation, Antigens, CD, Antigens, Viral, Biopolymers, Clone Cells, Cytotoxicity, Immunologic, DNA-Binding Proteins, HLA Antigens, HLA-A Antigens, HLA-B Antigens, HLA-C Antigens, Herpesvirus 4, Human, Histocompatibility Antigens Class I, Humans, Killer Cells, Natural, Lectins, C-Type, Membrane Glycoproteins, Mice, NK Cell Lectin-Like Receptor Subfamily D, Peptide Fragments, Protein Sorting Signals, Receptors, Antigen, T-Cell, alpha-beta, Recombinant Fusion Proteins, Trans-Activators, Transfection, Viral Proteins, beta 2-Microglobulin