MHC class I Dk locus and Ly49G2+ NK cells confer H-2k resistance to murine cytomegalovirus.
Essential NK cell-mediated murine CMV (MCMV) resistance is under histocompatibility-2(k) (H-2(k)) control in MA/My mice. We generated a panel of intra-H2(k) recombinant strains from congenic C57L.M-H2(k/b) (MCMV resistant) mice for precise genetic mapping of the critical interval. Recombination breakpoint sites were precisely mapped and MCMV resistance/susceptibility traits were determined for each of the new lines to identify the MHC locus. Strains C57L.M-H2(k)(R7) (MCMV resistant) and C57L.M-H2(k)(R2) (MCMV susceptible) are especially informative; we found that allelic variation in a 0.3-megabase interval in the class I D locus confers substantial difference in MCMV control phenotypes. When NK cell subsets responding to MCMV were examined, we found that Ly49G2(+) NK cells rapidly expand and selectively acquire an enhanced capacity for cytolytic functions only in C57L.M-H2(k)(R7). We further show that depletion of Ly49G2(+) NK cells before infection abrogated MCMV resistance in C57L.M-H2(k)(R7). We conclude that the MHC class I D locus prompts expansion and activation of Ly49G2(+) NK cells that are needed in H-2(k) MCMV resistance.
Xie
Xuefang
X
Department of Microbiology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
Stadnisky
Michael D
MD
Brown
Michael G
MG
D000818:Animals; D049109:Cell Proliferation; D006183:H-2 Antigens / Q000235:genetics* / Q000276:immunology; D015395:Histocompatibility Antigens Class I; D007109:Immunity; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D018146:Muromegalovirus / Q000276:immunology*; D055650:NK Cell Lectin-Like Receptor Subfamily A; D011995:Recombination, Genetic
D006183:H-2 Antigens; D015395:Histocompatibility Antigens Class I; C527095:Klra7 protein, mouse; D055650:NK Cell Lectin-Like Receptor Subfamily A