Synergized regulation of NK cell education by NKG2A and specific Ly49 family members
Xiaoqian Zhang,
Jin Feng,
Shasha Chen,
Haoyan Yang and
Zhongjun Dong ()
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Xiaoqian Zhang: Beijing Key Lab for Immunological Research on Chronic Diseases, Tsinghua University
Jin Feng: Beijing Key Lab for Immunological Research on Chronic Diseases, Tsinghua University
Shasha Chen: Beijing Key Lab for Immunological Research on Chronic Diseases, Tsinghua University
Haoyan Yang: Beijing Key Lab for Immunological Research on Chronic Diseases, Tsinghua University
Zhongjun Dong: Beijing Key Lab for Immunological Research on Chronic Diseases, Tsinghua University
Nature Communications, 2019, vol. 10, issue 1, 1-12
Abstract:
Abstract Mice lacking MHC class-I (MHC-I) display severe defects in natural killer (NK) cell functional maturation, a process designated as “education”. Whether self-MHC-I specific Ly49 family receptors and NKG2A, which are closely linked within the NK gene complex (NKC) locus, are essential for NK cell education is still unclear. Here we show, using CRISPR/Cas9-mediated gene deletion, that mice lacking all members of the Ly49 family exhibit a moderate defect in NK cell activity, while mice lacking only two inhibitory Ly49 members, Ly49C and Ly49I, have comparable phenotypes. Furthermore, the deficiency of NKG2A, which recognizes non-classical MHC-Ib molecules, mildly impairs NK cell function. Notably, the combined deletion of NKG2A and the Ly49 family severely compromises the ability of NK cells to mediate “missing-self” and “induced-self” recognition. Therefore, our data provide genetic evidence supporting that NKG2A and the inhibitory members of Ly49 family receptors synergize to regulate NK cell education.
Date: 2019
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13032-5
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DOI: 10.1038/s41467-019-13032-5
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