期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2010
卷号：107
期号：19
页码：8754-8759
DOI：10.1073/pnas.0913126107
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：NK cell-mediated murine cytomegalovirus (MCMV) resistance (Cmvr) is under H-2k control in MA/My mice, but the underlying gene(s) is unclear. Prior genetic analysis mapped Cmvr to the MHC class I (MHC-I) Dk gene interval. Because NK cell receptors are licensed by and responsive to MHC class I molecules, Dk itself is a candidate gene. A 10-kb genomic Dk fragment was subcloned and microinjected into MCMV-susceptible (Cmvs) (MA/My.L-H2b x C57L)F1 or (B6 x DBA/2)F2 embryos. Transgenic founders, which are competent for Dk expression and germline transgene transmission, were identified and further backcrossed to MA/My.L-H2b or C57L mice. Remarkably, Dk expression delivered NK-mediated resistance in either genetic background. Further, NK cells with cognate inhibitory Ly49G receptors for self-MHC-I Dk were licensed and critical in protection against MCMV infection. In radiation bone marrow chimeras, NK resistance was significantly diminished when MHC-I Dk expression was restricted to only hematopoietic or nonhematopoietic cells. Thus, MHC-I Dk is the H-2k-linked Cmvr locus; these findings suggest a role for NK cell interaction with Dk-bearing hematopoietic and nonhematopoietic cells to shape NK-mediated virus immunity.
