Retinoic acid early inducible genes define a ligand family for the activating NKG2D receptor in mice.
Here we describe a family of GPI-anchored cell surface proteins that function as ligands for the mouse activating NKG2D receptor. These molecules are encoded by the retinoic acid early inducible (RAE-1) and H60 minor histocompatibility antigen genes on mouse chromosome 10 and show weak homology with MHC class I. Expression of the NKG2D ligands is low or absent on normal, adult tissues; however, they are constitutively expressed on some tumors and upregulated by retinoic acid. Ectopic expression of RAE-1 and H60 confers target susceptibility to NK cell attack. These studies identify a family of ligands for the activating NKG2D receptor on NK and T cells, which may play an important role in innate and adaptive immunity.
Cerwenka
A
A
Department of Microbiology and Immunology and The Cancer Research Institute, University of California, San Francisco 94143, USA.
Bakker
A B
AB
McClanahan
T
T
Wagner
J
J
Wu
J
J
Phillips
J H
JH
Lanier
L L
LL
D000595:Amino Acid Sequence; D000818:Animals; D018827:Carcinoma, Lewis Lung; D003001:Cloning, Molecular / Q000379:methods; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics; D007074:Immunoglobulin G / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D008024:Ligands; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D015778:Minor Histocompatibility Antigens / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000276:immunology*; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D055607:Receptors, Natural Killer Cell; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D017261:Glycosylphosphatidylinositols; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; C527085:KLRK1 protein, human; C527086:Klrk1 protein, mouse; D008024:Ligands; D008565:Membrane Proteins; D015778:Minor Histocompatibility Antigens; D055655:NK Cell Lectin-Like Receptor Subfamily K; C491219:Raet1a protein, mouse; C491216:Raet1d, protein, mouse; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D011993:Recombinant Fusion Proteins; C114735:minor H antigen H60; D014212:Tretinoin