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RhCMV/SIV疫苗功效需要调节MHC-E的转运
作者:小柯机器人 发布时间:2021/3/28 16:22:06

美国俄勒冈卫生与科学大学Klaus Früh、Louis J. Picker等研究人员合作发现,RhCMV/SIV疫苗功效需要调节MHC-E的转运。该研究于2021年3月25日在线发表于国际一流学术期刊《科学》。

据研究人员介绍,表达猕猴免疫缺陷病毒(SIV)抗原的猕猴巨细胞病毒(RhCMV)68-1毒株能够引发CD8+T细胞识别由主要组织相容性复合物(MHC)-II和MHC-E而非MHC-1a呈递的表位。这些免疫反应介导了50%至60%猕猴中SIV的复制停滞。

研究人员表明,嵌入在RhCMV蛋白Rh67中的肽VMAPRTLLL(VL9)促进了细胞内MHC-E的运输以及由MHC-E限制的CD8+T细胞对RhCMV感染的成纤维细胞识别。病毒VL9的缺失或突变消除了MHC-E限制的CD8+T细胞活化,导致仅靶向MHC-II抗原决定簇的CD8+T细胞反应。

这些反应在强度和分化上与68-1载体引起的反应相当,但不能预防SIV。因此,Rh67使得MHC-E限制性T细胞的直接活化对于RhCMV/SIV疫苗功效至关重要。 

附:英文原文

Title: Modulation of MHC-E transport by viral decoy ligands is required for RhCMV/SIV vaccine efficacy

Author: Marieke Verweij, Scott G. Hansen, Ravi Iyer, Nessy John, Daniel Malouli, David Morrow, Isabel Scholz, Jennie Womack, Shaheed Abdulhaqq, Roxanne M. Gilbride, Colette M. Hughes, Abigail B. Ventura, Julia C. Ford, Andrea N. Selseth, Kelli Oswald, Rebecca Shoemaker, Brian Berkemeier, William J. Bosche, Michael Hull, Jason Shao, Jonah B. Sacha, Michael K. Axthelm, Paul T. Edlefsen, Jeffrey D. Lifson, Louis J. Picker, Klaus Früh

Issue&Volume: 2021/03/25

Abstract: Strain 68-1 rhesus cytomegalovirus (RhCMV) vectors expressing simian immunodeficiency virus (SIV) antigens elicit CD8+ T cells recognizing epitopes presented by major histocompatibility complex (MHC)-II and MHC-E, not MHC-Ia. These immune responses mediate replication arrest of SIV in 50 to 60% of monkeys. We show that the peptide VMAPRTLLL (VL9) embedded within the RhCMV protein Rh67 promotes intracellular MHC-E transport and recognition of RhCMV-infected fibroblasts by MHC-E-restricted CD8+ T cells. Deletion or mutation of viral VL9 abrogated MHC-E-restricted CD8+ T cell priming, resulting in CD8+ T cell responses exclusively targeting MHC-II-restricted epitopes. These responses were comparable in magnitude and differentiation to responses elicited by 68-1 vectors, but did not protect against SIV. Thus, Rh67-enabled direct priming of MHC-E-restricted T cells is crucial for RhCMV/SIV vaccine efficacy.

DOI: 10.1126/science.abe9233

Source: https://science.sciencemag.org/content/early/2021/03/24/science.abe9233

期刊信息
Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037