Direct binding of purified HLA class I antigens by soluble NKG2/CD94 C-type lectins from natural killer cells.
Human natural killer (NK) cell cytotoxicity is inhibited following human leucocyte antigen (HLA) class I binding by killer cell inhibitory receptors belonging to the immunoglobulin or C-type lectin protein families. Of the latter family, CD94 and NKG2A or -B associate to inhibit NK cell cytotoxicity. We have constructed C-Myc epitope-tagged soluble NKG2A, -B, -C, -D and human NKR-P1 lectin domains, and studied their ability to associate with Flu-tagged soluble CD94 lectin domains. Furthermore, their ability to bind solubilized immunoaffinity-purified HLA class I antigens, either alone or following association with CD94 lectin domains, was evaluated using flow cytometry and Western blot analyses. We show that soluble NKG2A, -B and -C lectin domains interact with CD94 lectin domains to form complexes, whereas NKG2D and human NKR-P1 lectin domains do not. Soluble NKG2C, -D and CD94 lectin domains bind solubilized affinity purified HLA class I antigens on their own, whereas NKG2A and -B require association with CD94 lectin domains for binding. Soluble human NKR-P1 lectin domains do not bind solubilized HLA class I antigens in our system.
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology*; D001665:Binding Sites; D019556:COS Cells; D015870:Gene Expression; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D037102:Lectins / Q000235:genetics / Q000276:immunology*; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D055651:NK Cell Lectin-Like Receptor Subfamily B; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology*; D055607:Receptors, Natural Killer Cell; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D012995:Solubility