Endogenous human cytomegalovirus gB is presented efficiently by MHC class II molecules to CD4+ CTL.
Endogenous human cytomegalovirus gB is presented efficiently by MHC class II molecules to CD4+ CTL.
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DOI：
10.1084/jem.20050162
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发表时间：
2005-10-17
期刊：
影响因子：
--
通讯作者：
Johnson DC
中科院分区：
文献类型：
--
作者：
Hegde NR;Dunn C;Lewinsohn DM;Jarvis MA;Nelson JA;Johnson DC
人巨细胞病毒（HCMV）在体内感染内皮细胞、上皮细胞和神经胶质细胞。这些细胞可以表达 MHC II 类蛋白，但不太可能在启动宿主免疫方面发挥重要作用。相反，这些细胞中内源 HCMV 抗原的 II 类呈递似乎可以识别病毒感染。我们对 HCMV 糖蛋白 B (gB) 的 II 类表达进行了表征，gB 是一种膜蛋白，在病毒组装过程中在内体中广泛积累。 gB 特异性的人 CD4+ T 细胞在血液中含量很高，并且在体内具有溶细胞作用。 gB 特异性 CD4+ T 细胞克隆识别在神经胶质细胞、内皮细胞和上皮细胞中表达的 gB，但不识别供给这些细胞的外源 gB。胶质细胞有效地呈现极低水平的内源性 gB（由腺病毒载体表达或在 HCMV 感染后表达），并且比与外源性 gB 一起孵育的 DC 更好地刺激 CD4+ T 细胞。内源性 gB 的呈现需要将 gB 分选至内体区室并通过酸性蛋白酶进行处理。尽管输送到内体的细胞蛋白的呈递是众所周知的，但我们的观察首次证明分选到内体的病毒蛋白的呈递效果非常好，并且可以促进 CD4+ T 细胞识别和杀死具有生物学重要意义的宿主细胞。
Human cytomegalovirus (HCMV) infects endothelial, epithelial, and glial cells in vivo. These cells can express MHC class II proteins, but are unlikely to play important roles in priming host immunity. Instead, it seems that class II presentation of endogenous HCMV antigens in these cells allows recognition of virus infection. We characterized class II presentation of HCMV glycoprotein B (gB), a membrane protein that accumulates extensively in endosomes during virus assembly. Human CD4+ T cells specific for gB were both highly abundant in blood and cytolytic in vivo. gB-specific CD4+ T cell clones recognized gB that was expressed in glial, endothelial, and epithelial cells, but not exogenous gB that was fed to these cells. Glial cells efficiently presented extremely low levels of endogenous gB—expressed by adenovirus vectors or after HCMV infection—and stimulated CD4+ T cells better than DCs that were incubated with exogenous gB. Presentation of endogenous gB required sorting of gB to endosomal compartments and processing by acidic proteases. Although presentation of cellular proteins that traffic into endosomes is well known, our observations demonstrate for the first time that a viral protein sorted to endosomes is presented exceptionally well, and can promote CD4+ T cell recognition and killing of biologically important host cells.
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