A Viral Immunoevasin Controls Innate Immunity by Targeting the Prototypical Natural Killer Cell Receptor Family

被引：66

作者：

Aguilar, Oscar A. ^{[1
,2
]}

Berry, Richard ^{[3
,6
]}

Rahim, Mir Munir A. ^{[4
,9
]}

Reichel, Johanna J. ^{[5
]}

Popovic, Branka ^{[5
]}

Tanaka, Miho ^{[1
,2
]}

Fu, Zhihui ^{[3
]}

Balaji, Gautham R. ^{[3
,6
]}

Lau, Timothy N. H. ^{[1
,2
]}

Tu, Megan M. ^{[4
]}

Kirkham, Christina L. ^{[1
,2
]}

Mahmoud, Ahmad Bakur ^{[4
,8
]}

Mesci, Aruz ^{[1
,2
]}

Krmpotic, Astrid ^{[5
]}

Allan, David S. J. ^{[1
,2
,10
]}

Makrigiannis, Andrew P. ^{[4
,9
]}

Jonjic, Stipan ^{[5
]}

Rossjohn, Jamie ^{[3
,7
]}

Carlyle, James R. ^{[1
,2
]}

机构：

[1] Univ Toronto, Dept Immunol, Toronto, ON M5S 1A8, Canada

[2] Sunnybrook Res Inst, Toronto, ON M4N 3M5, Canada

[3] Monash Univ, Biomed Discovery Inst, Dept Biochem & Mol Biol, Infect & Immun Program, Clayton, Vic 3800, Australia

[4] Univ Ottawa, Dept Biochem Microbiol & Immunol, Ottawa, ON K1H 8M5, Canada

[5] Univ Rijeka, Dept Histol & Embryol, Fac Med, Rijeka 51000, Croatia

[6] Monash Univ, ARC Ctr Excellence Adv Mol Imaging, Clayton, Vic 3800, Australia

[7] Cardiff Univ, Inst Infect & Immun, Sch Med, Heath Pk, Cardiff CF14 4XN, S Glam, Wales

[8] Taibah Univ, Coll Appl Med Sci, Madinah Munawwarah 30001, Saudi Arabia

[9] Dalhousie Univ, Dept Microbiol & Immunol, Halifax, NS B3H 4R2, Canada

[10] NHLBI, NIH, Bethesda, MD 20892 USA

来源：

CELL | 2017年 / 169卷 / 01期

基金：

欧洲研究理事会; 英国医学研究理事会; 澳大利亚研究理事会; 加拿大健康研究院; 加拿大自然科学与工程研究理事会;

关键词：

MISSING-SELF-RECOGNITION; MURINE CYTOMEGALOVIRUS-INFECTION; NK GENE-COMPLEX; NKR-P1; RECEPTORS; NK1.1; ANTIGEN; MOUSE; EXPRESSION; REVEALS; RECOMBINATION; PATHOGENS;

D O I：

10.1016/j.cell.2017.03.002

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Natural killer (NK) cells play a key role in innate immunity by detecting alterations in self and non-self ligands via paired NK cell receptors (NKRs). Despite identification of numerous NKR-ligand interactions, physiological ligands for the prototypical NK1.1 orphan receptor remain elusive. Here, we identify a viral ligand for the inhibitory and activating NKRP1 (NK1.1) receptors. This murine cytomegalovirus (MCMV)-encoded protein, m12, restrains NK cell effector function by directly engaging the inhibitory NKR-P1B receptor. However, m12 also interacts with the activating NKR-P1A/ C receptors to counterbalance m12 decoy function. Structural analyses reveal that m12 sequesters a large NKR-P1 surface area via a `` polar claw'' mechanism. Polymorphisms in, and ablation of, the viral m12 protein and host NKR-P1B/ C alleles impact NK cell responses in vivo. Thus, we identify the long-sought foreign ligand for this key immunoregulatory NKR family and reveal how it controls the evolutionary balance of immune recognition during host-pathogen interplay.

引用

页码：58 / +

页数：28

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