title: Mouse NK cell-mediated rejection of bone marrow allografts exhibits patterns consistent with Ly49 subset licensing.
abstract: Natural killer (NK) cells can mediate the rejection of bone marrow allografts and exist as subsets based on expression of inhibitory/activating receptors that can bind MHC. In vitro data have shown that NK subsets bearing Ly49 receptors for self-MHC class I have intrinsically higher effector function, supporting the hypothesis that NK cells undergo a host MHC-dependent functional education. These subsets also play a role in bone marrow cell (BMC) allograft rejection. Thus far, little in vivo evidence for this preferential licensing across mouse strains with different MHC haplotypes has been shown. We assessed the intrinsic response potential of the different Ly49(+) subsets in BMC rejection by using β2-microglobulin deficient (β2m(-/-)) mice as donors. Using congenic and allogeneic mice as recipients and depleting the different Ly49 subsets, we found that NK subsets bearing Ly49s, which bind "self-MHC" were found to be the dominant subset responsible for β2m(-/-) BMC rejection. This provides in vivo evidence for host MHC class I-dependent functional education. Interestingly, all H2(d) strain mice regardless of background were able to resist significantly greater amounts of β2m(-/-), but not wild-type BMC than H2(b) mice, providing evidence that the rheostat hypothesis regarding Ly49 affinities for MHC and NK-cell function impacts BMC rejection capability.
authors.affiliation: Department of Dermatology, School of Medicine, University of California-Davis, 2921 Stockton Blvd., Sacramento, CA 95817, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Sun
authors.forename: Maite
authors.initials: M
authors.lastname: Alvarez
authors.forename: Erik
authors.initials: E
authors.lastname: Ames
authors.forename: Isabel
authors.initials: I
authors.lastname: Barao
authors.forename: Mingyi
authors.initials: M
authors.lastname: Chen
authors.forename: Dan L
authors.initials: DL
authors.lastname: Longo
authors.forename: Doug
authors.initials: D
authors.lastname: Redelman
authors.forename: William J
authors.initials: WJ
authors.lastname: Murphy
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000276:immunology* / Q000379:methods; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006183:H-2 Antigens / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D055650:NK Cell Lectin-Like Receptor Subfamily A / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D014184:Transplantation, Homologous; D001613:beta 2-Microglobulin / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D006183:H-2 Antigens; D055650:NK Cell Lectin-Like Receptor Subfamily A; D001613:beta 2-Microglobulin