Murine cytomegalovirus downregulates ERAAP and induces an unconventional T cell response to self.
Murine cytomegalovirus downregulates ERAAP and induces an unconventional T cell response to self.
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DOI：
10.1016/j.celrep.2023.112317
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发表时间：
2023-04-25
期刊：
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
与抗原加工相关的内质网氨基肽酶(ERAAP)在形成主要组织相容性复合体(MHC)I类谱系和维持免疫监视方面起着至关重要的作用。虽然小鼠巨细胞病毒(MCMV)有多种策略来操纵抗原处理途径来逃避免疫反应，但宿主也开发出了对抗病毒免疫逃避的方法。在这项研究中，我们发现巨细胞病毒调节ERAAP，并诱导产生干扰素γ(干扰素-γ)的CD8+T细胞效应反应，以未感染的ERAAP缺陷细胞为靶点。我们观察到，感染过程中ERAAP下调导致非经典Qa-1b上出现自肽Fl9，从而诱导Qa-1b限制的QFL T细胞在感染小鼠的肝和脾中增殖。QFL T细胞在MCMV感染时上调效应标记，并在转移到免疫缺陷小鼠后足以降低病毒载量。我们的研究强调了病毒感染过程中ERAAP功能障碍的后果，并为抗病毒治疗提供了潜在的靶点。Geiger等人。发现MCMV下调MHC-I类多肽加工酶ERAAP的表达。感染MCMV的小鼠产生一种非经典的QFL T细胞反应，针对ERAAP下调的细胞。QFL T细胞对免疫缺陷小鼠严重的MCMV感染具有保护作用。QFL T细胞是对抗MCMV感染的一种非常规免疫反应。
The endoplasmic reticulum aminopeptidase associated with antigen processing (ERAAP) plays a crucial role in shaping the peptide-major histocompatibility complex (MHC) class I repertoire and maintaining immune surveillance. While murine cytomegalovirus (MCMV) has multiple strategies for manipulating the antigen processing pathway to evade immune responses, the host has also developed ways to counter viral immune evasion. In this study, we find that MCMV modulates ERAAP and induces an interferon γ (IFN-γ)-producing CD8+ T cell effector response that targets uninfected ERAAP-deficient cells. We observe that ERAAP downregulation during infection leads to the presentation of the self-peptide FL9 on non-classical Qa-1b, thereby eliciting Qa-1b-restricted QFL T cells to proliferate in the liver and spleen of infected mice. QFL T cells upregulate effector markers upon MCMV infection and are sufficient to reduce viral load after transfer to immunodeficient mice. Our study highlights the consequences of ERAAP dysfunction during viral infection and provides potential targets for anti-viral therapies. Geiger et al. find that MCMV downregulates MHC class I peptide-processing enzyme ERAAP. MCMV-infected mice develop a non-classical QFL T cell response, directed against ERAAP downregulated cells. QFL T cells protect against severe MCMV infection in immunodeficient mice. QFL T cells serve as an unconventional response against MCMV infection.
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人CD8+ T细胞响应的效率：我们应该如何量化它，什么决定它，这有关系？
影响因子：
4.3
作者：
Elemans M;Seich Al Basatena NK;Asquith B
通讯作者：
Asquith B
DOI：
10.1126/science.aac9475
发表时间：
2016-02-12
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hansen SG;Wu HL;Burwitz BJ;Hughes CM;Hammond KB;Ventura AB;Reed JS;Gilbride RM;Ainslie E;Morrow DW;Ford JC;Selseth AN;Pathak R;Malouli D;Legasse AW;Axthelm MK;Nelson JA;Gillespie GM;Walters LC;Brackenridge S;Sharpe HR;López CA;Früh K;Korber BT;McMichael AJ;Gnanakaran S;Sacha JB;Picker LJ
通讯作者：
Picker LJ
影响因子：
64.8
作者：
Hansen, Scott G.;Ford, Julia C.;Lewis, Matthew S.;Ventura, Abigail B.;Hughes, Colette M.;Coyne-Johnson, Lia;Whizin, Nathan;Oswald, Kelli;Shoemaker, Rebecca;Swanson, Tonya;Legasse, Alfred W.;Chiuchiolo, Maria J.;Parks, Christopher L.;Axthelm, Michael K.;Nelson, Jay A.;Jarvis, Michael A.;Piatak, Michael, Jr.;Lifson, Jeffrey D.;Picker, Louis J.
通讯作者：
Picker, Louis J.
影响因子：
29.7
作者：
Blum JS;Wearsch PA;Cresswell P
通讯作者：
Cresswell P
影响因子：
30.5
作者：
Hammer, GE;Gonzalez, F;Shastri, N
通讯作者：
Shastri, N