Inhibition of major histocompatibility complex Class 1 antigen presentation by hepatitis C virus core protein in myeloid dendritic cells
Inhibition of major histocompatibility complex Class 1 antigen presentation by hepatitis C virus core protein in myeloid dendritic cells
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DOI：
10.1016/j.virol.2009.03.035
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发表时间：
2009-06-01
期刊：
影响因子：
3.7
通讯作者：
Harrison, Phillip M.
中科院分区：
文献类型：
--
作者：
O'Beirne, James;Mitchell, Jon;Harrison, Phillip M.
通过电穿孔丙型肝炎病毒核心（HCVcore）mRNA在来自C57/B6小鼠（H-2K（B））的髓样树突状细胞（DC）中表达HCVcore蛋白，以研究其对DC致敏展示对OVA（257-264）肽（SIINFEKL）/H-2K（B）复合物特异性的T细胞受体的CD 8 + T细胞的能力的影响。表达全长HCV核心（191），其通过C-末端信号序列导向内质网（ER）膜，但不表达截短的变体HCV核心（152），其具有更宽的亚细胞定位，包括细胞核，显著降低了H-2K（B）/SIINFEKL复合物的表面水平，并损害了DC致敏幼稚CD 8+的能力。当T细胞必须处理内源性抗原时，它们对SIINFEKL肽的反应性降低，但当MHC I类分子直接负载SIINFEKL肽时则没有。HCVcore（191）对MHC I类抗原加工途径的利用削弱了DC刺激CD 8 + T细胞的能力，并可能导致HCV感染的持续。(c)2009爱思唯尔公司All rights reserved.
Hepatitis C virus core (HCVcore) protein was expressed in myeloid dendritic cells (DC) from C57/B6 mice (H-2K(b)) by electroporation of HCVcore mRNA to investigate its effect on the ability of DC to prime CD8+ T cells displaying a T cell receptor specific for OVA(257-264) peptide (SIINFEKL)/H-2K(b) complex. Expression of full length HCVcore(191), which is directed to the endoplasmic reticulum (ER) membrane by a C-terminal signal sequence, but not a truncated variant HCVcore(152), which has a wider subcellular localization including the nucleus, significantly reduced surface levels of the H-2K(b)/SIINFEKL complex and impaired the ability of DC to prime naive CD8+ T cells when they had to process endogenous antigen but not when MHC class I molecules were loaded directly with SIINFEKL peptide. Exploitation of the MHC class I antigen-processing pathway by HCVcore(191) impairs the ability of DC to stimulate CD8+ T cells and may contribute to the persistence of HCV infection. (c) 2009 Elsevier Inc. All rights reserved.