NK cell CD94/NKG2A inhibitory receptors are internalized and recycle independently of inhibitory signaling processes.
Human CD94/NKG2A is an inhibitory receptor that recognizes HLA-E and is expressed by NK cells and a subset of T cells. We have analyzed the cellular trafficking of the CD94/NKG2A receptor using the NKL cell line and peripheral blood NK cells. Flow cytometric, confocal microscopic, and biochemical analyses show that CD94/NKG2A continuously recycles in an active process that requires the cytoskeleton between the cell surface and intracellular compartments that are distinguishable from recycling compartments used by well-characterized receptors, such as transferrin receptor (CD71). CD94/NKG2A, an inhibitory receptor, traffics differently from the closely related CD94/NKG2C molecule, an activating receptor. Using transfection/expression analyses of wild-type and mutant CD94/NKG2A molecules in the HLA-E negative rat basophilic cell line RBL-2H3, we demonstrate that CD94/NKG2A internalization is independent of ligand cross-linking or the presence of functional immunoreceptor tyrosine-based inhibition motifs. Thus, the mechanisms that control cell surface homeostasis of CD94/NKG2A are independent of functional signaling.
Borrego
Francisco
F
Receptor Cell Biology Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA. Fborrego@niaid.nih.gov
Kabat
Juraj
J
Sanni
Tolib B
TB
Coligan
John E
JE
D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D002451:Cell Compartmentation; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D003599:Cytoskeleton / Q000276:immunology / Q000378:metabolism; D004734:Energy Metabolism; D006680:HLA Antigens / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D009154:Mutation; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D051381:Rats; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D055607:Receptors, Natural Killer Cell; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D000097625:HLA-E Antigens
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D037181:Lectins, C-Type; D008024:Ligands; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D011994:Recombinant Proteins; D000097625:HLA-E Antigens; C527054:KLRC1 protein, human; C527059:KLRC2 protein, human; C497869:KLRD1 protein, human; C527057:Klrc1 protein, mouse; C527060:Klrc2 protein, mouse; C497870:Klrd1 protein, mouse; C497871:Klrd1 protein, rat