Abstract
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.
MeSH terms
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Animals
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Antibodies, Monoclonal
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Antigens, CD / genetics
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Antigens, CD / metabolism*
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Cell Compartmentation
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Cell Line
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Cell Membrane / immunology
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Cell Membrane / metabolism
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Cytoskeleton / immunology
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Cytoskeleton / metabolism
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Energy Metabolism
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HLA Antigens / metabolism
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HLA-E Antigens
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Histocompatibility Antigens Class I / metabolism
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Humans
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Killer Cells, Natural / immunology*
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Killer Cells, Natural / metabolism
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Lectins, C-Type / genetics
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Lectins, C-Type / metabolism*
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Ligands
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Mice
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Mutation
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NK Cell Lectin-Like Receptor Subfamily C
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NK Cell Lectin-Like Receptor Subfamily D
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Rats
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Receptors, Immunologic / genetics
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Receptors, Immunologic / metabolism*
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Receptors, Natural Killer Cell
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Signal Transduction
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Transfection
Substances
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Antibodies, Monoclonal
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Antigens, CD
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HLA Antigens
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Histocompatibility Antigens Class I
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KLRC1 protein, human
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KLRC2 protein, human
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KLRD1 protein, human
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Klrc1 protein, mouse
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Klrc2 protein, mouse
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Klrd1 protein, mouse
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Klrd1 protein, rat
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Lectins, C-Type
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Ligands
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NK Cell Lectin-Like Receptor Subfamily C
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NK Cell Lectin-Like Receptor Subfamily D
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Receptors, Immunologic
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Receptors, Natural Killer Cell
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Recombinant Proteins