Journal Article

Synergized regulation of NK cell education by NKG2A and specific Ly49 family members

Dong, Zhongjun, Zhang, Xiaoqian, Yang, Haoyan, Feng, Jin, Chen, Shasha

2019

Overview

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. MHC-I-induced signalling of various natural killer (NK) inhibitory receptors is critical for regulation NK cell education, but clear genetic evidence is still lacking. Here the authors generate multiple lines of mice differentially deficient in Ly49 family and/or NKG2A NK receptors, and find that self-MHCI specific Ly49 members and NKG2A synergize to regulate NK education.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 38/1 / 42/41 / 45/23 / 631/250/1619/382 / 631/250/248 / 631/250/38 / 631/250/580/1884 / 64/60 / Animals / Clonal deletion / CRISPR / CRISPR-Cas Systems / Education / Gene deletion / Gene Editing - methods / Histocompatibility Antigens Class I - genetics / Histocompatibility Antigens Class I - immunology / Histocompatibility Antigens Class I - metabolism / Humanities and Social Sciences / Killer Cells, Natural - immunology / Killer Cells, Natural - metabolism / Ly-49 antigen / Major histocompatibility complex / Mice, Inbred C57BL / Mice, Inbred NOD / Mice, Knockout / Mice, SCID / multidisciplinary / Multigene Family / Mushrooms / Natural killer cells / NK Cell Lectin-Like Receptor Subfamily A - genetics / NK Cell Lectin-Like Receptor Subfamily A - immunology / NK Cell Lectin-Like Receptor Subfamily A - metabolism / NK Cell Lectin-Like Receptor Subfamily C - genetics / NK Cell Lectin-Like Receptor Subfamily C - immunology / NK Cell Lectin-Like Receptor Subfamily C - metabolism / NKG2 antigen / Phenotypes / Receptors / Science / Science (multidisciplinary) / Synergism