Specificity and function of activating Ly-49 receptors.
Inhibitory Ly-49 receptors allow murine natural killer (NK) cells to kill cells with aberrant class I MHC expression while sparing normal cells. This is accomplished by their recognition of specific class I MHC products and prevention of NK-cell lysis of cells that present a normal repertoire of class I MHC ligands--"the missing self hypothesis". However, Ly-49 receptors that lack the cytoplasmic immunoreceptor tyrosine-based inhibitory motif, which is required for inhibition of killing, have also been described. These receptors were found to stimulate NK killing and are therefore referred to as activating Ly-49 receptors. Interestingly, the activating receptors have class I MHC-binding domains that are nearly indistinguishable from those of the inhibiting receptors, and binding to class I MHC has now been demonstrated for three activating receptors. Presently, there is no defined physiological role for activating Ly-49 receptors. Here we present an overview of current knowledge regarding the diversity, structure and function of activating Ly-49 receptors with a focus on class I MHC specificity, and we discuss their potential role(s) in natural resistance.
Kane
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Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Canada. kevin.kane@ualberta.ca
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D000818:Animals; D000950:Antigens, Ly; D001665:Binding Sites; D015870:Gene Expression; D014644:Genetic Variation; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type; D008024:Ligands; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D008958:Models, Molecular; D005810:Multigene Family; D010802:Phylogeny; D055630:Receptors, NK Cell Lectin-Like; D015398:Signal Transduction
D000950:Antigens, Ly; D015395:Histocompatibility Antigens Class I; D037181:Lectins, C-Type; D008024:Ligands; D008562:Membrane Glycoproteins; D055630:Receptors, NK Cell Lectin-Like