Peptide-specific recognition of human cytomegalovirus strains controls adaptive natural killer cells

Hammer Quirin; Rueckert Timo; Borst Eva Maria; Dunst Josefine; Haubner Andre; Durek Pawel; Heinrich Frederik; Gasparoni Gilles; Babic Marina; Tomic Adriana; Pietra Gabriella; Nienen Mikalai; Blau Igor Wolfgang; Hofmann Joerg; Na Il-Kang; Prinz Immo; Koenecke Christian; Hemmati Philipp; Babel Nina; Arnold Renate; Walter Joern; Thurley Kevin; Mashreghi Mir-Farzin; Messerle Martin; Romagnani Chiara

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Peptide-specific recognition of human cytomegalovirus strains controls adaptive natural killer cells

机译：人巨细胞病毒菌株的肽特异性识别控制适应性天然杀伤细胞

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Natural killer (NK) cells are innate lymphocytes that lack antigen-specific rearranged receptors, a hallmark of adaptive lymphocytes. In some people infected with human cytomegalovirus (HCMV), an NK cell subset expressing the activating receptor NKG2C undergoes clonal-like expansion that partially resembles anti-viral adaptive responses. However, the viral ligand that drives the activation and differentiation of adaptive NKG2C(+) NK cells has remained unclear. Here we found that adaptive NKG2C(+) NK cells differentially recognized distinct HCMV strains encoding variable UL40 peptides that, in combination with pro-inflammatory signals, controlled the population expansion and differentiation of adaptive NKG2C(+) NK cells. Thus, we propose that polymorphic HCMV peptides contribute to shaping of the heterogeneity of adaptive NKG2C(+) NK cell populations among HCMV-seropositive people.

机译：天然杀手（NK）细胞是先天淋巴细胞，缺乏抗原特异性重排受体，适应性淋巴细胞的标志。在某些人感染人巨细胞病毒（HCMV）中，表达活化受体NKG2C的NK细胞子被经历克隆类似的膨胀，其部分类似于抗病毒适应性反应。然而，驱动自适应NKG2C（+）NK细胞的活化和分化的病毒配体仍然不清楚。在这里，我们发现适应性NKG2C（+）NK细胞差异识别的不同HCMV菌株编码可变UL40肽，与促炎信号组合，控制了适应性NKG2C（+）NK细胞的群体膨胀和分化。因此，我们提出多晶型HCMV肽有助于在HCMV-血清阳性人中的适应性NKG2C（+）NK细胞群的异质性。

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《Nature immunology》 |2018年第5期|共14页
作者
Hammer Quirin; Rueckert Timo; Borst Eva Maria; Dunst Josefine; Haubner Andre; Durek Pawel; Heinrich Frederik; Gasparoni Gilles; Babic Marina; Tomic Adriana; Pietra Gabriella; Nienen Mikalai; Blau Igor Wolfgang; Hofmann Joerg; Na Il-Kang; Prinz Immo; Koenecke Christian; Hemmati Philipp; Babel Nina; Arnold Renate; Walter Joern; Thurley Kevin; Mashreghi Mir-Farzin; Messerle Martin; Romagnani Chiara;
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Leibniz Assoc German Rheumatism Res Ctr DRFZ Innate Immun Berlin Germany;

Leibniz Assoc German Rheumatism Res Ctr DRFZ Innate Immun Berlin Germany;

Hannover Med Sch Inst Virol Hannover Germany;

Leibniz Assoc German Rheumatism Res Ctr DRFZ Inflammat Biol Berlin Germany;

Leibniz Assoc German Rheumatism Res Ctr DRFZ Innate Immun Berlin Germany;

Leibniz Assoc German Rheumatism Res Ctr DRFZ Cell Biol Berlin Germany;

Leibniz Assoc Therapeut Gene Regulat German Rheumatism Res Ctr Berlin Germany;

Univ Saarland Dept Genet Saarbrucken Germany;

Leibniz Assoc German Rheumatism Res Ctr DRFZ Innate Immun Berlin Germany;

Hannover Med Sch Inst Virol Hannover Germany;

Univ Genoa Dept Expt Med Genoa Italy;

Ruhr Univ Bochum Marien Hosp Herne Med Clin 1 Herne Germany;

Charite Dept Hematol Oncol &

Tumor Immunol Berlin Germany;

Charite Inst Virol Berlin Germany;

Charite Dept Hematol Oncol &

Tumor Immunol Berlin Germany;

Hannover Med Sch Inst Immunol Hannover Germany;

Hannover Med Sch Inst Immunol Hannover Germany;

Charite Dept Hematol Oncol &

Tumor Immunol Berlin Germany;

Ruhr Univ Bochum Marien Hosp Herne Med Clin 1 Herne Germany;

Charite Dept Hematol Oncol &

Tumor Immunol Berlin Germany;

Univ Saarland Dept Genet Saarbrucken Germany;

Leibniz Assoc German Rheumatism Res Ctr DRFZ Syst Biol Inflammat Berlin Germany;

Leibniz Assoc Therapeut Gene Regulat German Rheumatism Res Ctr Berlin Germany;

Hannover Med Sch Inst Virol Hannover Germany;

Leibniz Assoc German Rheumatism Res Ctr DRFZ Innate Immun Berlin Germany;

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专利

1. Peptide-specific recognition of human cytomegalovirus strains controls adaptive natural killer cells [J] . Hammer Quirin, Rueckert Timo, Borst Eva Maria, Nature immunology . 2018,第5期

机译：人巨细胞病毒菌株的肽特异性识别控制适应性天然杀伤细胞
2. A Cytomegalovirus Peptide-Specific Antibody Alters Natural Killer Cell Homeostasis and Is Shared in Several Autoimmune Diseases [J] . Liu Yu, Mu Rong, Gao Ya-Ping, Cell Host & Microbe . 2016,第3期

机译：巨细胞病毒肽特异的抗体改变自然杀伤细胞稳态，并在几种自身免疫性疾病中共享。
3. Activation of hepatic natural killer cells and control of liver-adapted lymphoma in the murine model of cytomegalovirus infection [J] . Katja C. Erlach, Verena Böhm, Martin Knabe, Medical Microbiology and Immunology . 2008,第2期

机译：巨细胞病毒感染小鼠模型中肝自然杀伤细胞的活化和肝适应性淋巴瘤的控制
4. GENERATION OF NATURAL KILLER CELLS FROM SERUM-FREE EXPANDED CD34~+ CELLS ISOLATED FROM HUMAN UMBILICAL CORD BLOOD [C] . I-Ting Kao, Zwe-Ling Kong, Mei-Ling Wu, Annual Meeting of the Japanese Association for Animal Cell Technology . 2006

机译：从无血清膨胀的CD34〜+细胞中产生自然杀伤细胞的产生从人脐带血中分离的细胞
5. Molecular basis of cancer cell recognition and killing by human natural killer cells. [D] . Boles, Kent Stewart. 2001

机译：癌细胞被人类自然杀伤细胞识别和杀死的分子基础。
6. Polymorphism in Human Cytomegalovirus UL40 Impacts on Recognition of Human Leukocyte Antigen-E (HLA-E) by Natural Killer Cells [O] . Susan L. Heatley, Gabriella Pietra, Jie Lin, 2013

机译：人类巨细胞病毒UL40的多态性影响自然杀伤细胞对人类白细胞抗原-E（HLA-E）的识别
7. Adaptive Natural Killer Cell and Killer Cell Immunoglobulin–Like Receptor–Expressing T Cell Responses are Induced by Cytomegalovirus and Are Associated with Protection against Cytomegalovirus Reactivation after Allogeneic Donor Hematopoietic Cell Transplantation [O] . Davis Zachary B., Cooley Sarah A., Cichocki Frank, 2015

机译：适应性天然杀伤细胞和表达杀伤细胞免疫球蛋白样受体的T细胞反应是由巨细胞病毒诱导的，并且与同种异体供体造血细胞移植后对巨细胞病毒再激活的保护有关。

Peptide-specific recognition of human cytomegalovirus strains controls adaptive natural killer cells

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