MHC class I cross-presentation by dendritic cells counteracts viral immune evasion
MHC class I cross-presentation by dendritic cells counteracts viral immune evasion
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DOI：
10.3389/fimmu.2012.00348
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发表时间：
2012-01-01
影响因子：
7.3
通讯作者：
Brocker, Thomas
中科院分区：
文献类型：
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作者：
Nopora, Katrin;Bernhard, Caroline A.;Brocker, Thomas
dc非常有效地激活CD8(+) T细胞特异性的病毒肽结合MHC I类分子。然而，许多病毒已经进化出免疫逃避机制，使感染的dc失活，并可能减少T细胞的启动。因此，非感染dc与外源性病毒Ag的MHC I类交叉表达可能成为确保CD8(+) T细胞应答的关键。尽管受感染的dc的许多重要功能在体外被许多不同的病毒抑制，但在体内面对病毒免疫失活时，交叉呈递对T细胞免疫的贡献迄今尚未得到证实，并且仍然存在争议。本研究表明，在dc特异性交叉呈现缺陷的小鼠中，单纯疱疹病毒（HSV）而非小鼠巨细胞病毒（mCMV）特异性CD8(+) T细胞的启动严重减少。相比之下，虽然CD8(+) T细胞对缺乏关键抑制基因的突变型HSV的反应也依赖于CD8 α (+) dc，但它们独立于交叉呈递。因此，单纯疱疹病毒特异性的c应答完全依赖于CD8 α (+) DC亚群，其通过直接或交叉呈递机制呈现，这取决于病毒的免疫逃避设备。我们的数据确定了交叉呈现的贡献，以抵消一些病毒的免疫逃避机制，但不是所有的病毒。
DCs very potently activate CD8(+) T cells specific for viral peptides bound to MHC class I molecules. However, many viruses have evolved immune evasion mechanisms, which inactivate infected DCs and might reduce priming of T cells. Then MHC class I crosspresentation of exogenous viral Ag by non-infected DCs may become crucial to assure CD8(+) T cell responses. Although many vital functions of infected DCs are inhibited in vitro by many different viruses, the contributions of cross-presentation to T cell immunity when confronted with viral immune inactivation in vivo has not been demonstrated up to now, and remains controversial. Here we show that priming of Herpes Simplex Virus (HSV), but not murine cytomegalovirus (mCMV)-specific CD8(+) T cells was severely reduced in mice with a DC-specific cross-presentation deficiency. In contrast, while CD8(+) T cell responses to mutant HSV, which lacks crucial inhibitory genes, also depended on CD8 alpha(+) DCs, they were independent of cross-presentation. Therefore HSV-specific CThresponses entirely depend on the CD8 alpha(+) DC subset, which present via direct or cross-presentation mechanisms depending on the immune evasion equipment of virus. Our data establish the contribution of cross-presentation to counteract viral immune evasion mechanisms in some, but not all viruses.