title: Skewing of the NK cell repertoire by MHC class I via quantitatively controlled enrichment and contraction of specific Ly49 subsets.
abstract: A major task for the immune system is to secure powerful immune reactions while preserving self-tolerance. This process is particularly challenging for NK cells, for which tolerizing inhibitory receptors for self-MHC class I is both cross-reactive and expressed in an overlapping fashion between NK cells. We show in this study that during an education process, self-MHC class I molecules enrich for potentially useful and contract potentially dangerous NK cell subsets. These processes were quantitatively controlled by the expression level of the educating MHC class I allele, correlated with susceptibility to IL-15 and sensitivity to apoptosis in relevant NK cell subsets, and were linked to their functional education. Controlling the size of NK cell subsets with unique compositions of inhibitory receptors may represent one mechanism by which self-MHC class I molecules generate a population of tolerant NK cells optimally suited for efficient missing self-recognition.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, S-17177 Stockholm, Sweden. petter.brodin@ki.se
authors.forename: Petter
authors.initials: P
authors.lastname: Brodin
authors.forename: Tadepally
authors.initials: T
authors.lastname: Lakshmikanth
authors.forename: Klas
authors.initials: K
authors.lastname: Kärre
authors.forename: Petter
authors.initials: P
authors.lastname: Höglund
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006183:H-2 Antigens / Q000096:biosynthesis* / Q000235:genetics; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D055650:NK Cell Lectin-Like Receptor Subfamily A / Q000096:biosynthesis / Q000172:deficiency / Q000276:immunology*
chemical_list: D006183:H-2 Antigens; D055650:NK Cell Lectin-Like Receptor Subfamily A