Cutting edge: lectin-like transcript-1 is a ligand for the inhibitory human NKR-P1A receptor.
Increasingly, roles are emerging for C-type lectin receptors in immune regulation. One receptor whose function has remained largely enigmatic is human NKR-P1A (CD161), present on NK cells and subsets of T cells. In this study, we demonstrate that the lectin-like transcript-1 (LLT1) is a physiologic ligand for NKR-P1A. LLT1-containing liposomes bind to NKR-P1A+ cells, and binding is inhibited by anti-NKR-P1A mAb. Additionally, LLT1 activates NFAT-GFP reporter cells expressing a CD3zeta-NKR-P1A chimeric receptor; reciprocally, reporter cells with a CD3zeta-LLT1 chimeric receptor are stimulated by NKR-P1A. Moreover, LLT1 on target cells can inhibit NK cytotoxicity via interactions with NKR-P1A.
Rosen
David B
DB
Department of Microbiology and Immunology, The Cancer Research Institute, and Biomedical Sciences Graduate Program, University of California, San Francisco, CA 94143, USA.
Bettadapura
Jayaram
J
Alsharifi
Mohammed
M
Mathew
Porunelloor A
PA
Warren
Hilary S
HS
Lanier
Lewis L
LL
D000818:Animals; D000954:Antigens, Surface / Q000276:immunology / Q000378:metabolism*; D017252:CD3 Complex / Q000235:genetics; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism*; D008024:Ligands; D008081:Liposomes; D008213:Lymphocyte Activation; D051379:Mice; D050778:NFATC Transcription Factors / Q000235:genetics; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000378:metabolism; D014162:Transfection
D000954:Antigens, Surface; D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; C400041:CLEC2D protein, human; C527203:KLRB1 protein, human; D037181:Lectins, C-Type; D008024:Ligands; D008081:Liposomes; D050778:NFATC Transcription Factors; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins