A CD74-dependent MHC class I endolysosomal cross-presentation pathway.
A CD74-dependent MHC class I endolysosomal cross-presentation pathway.
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DOI：
10.1038/ni.2225
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发表时间：
2012-02-05
影响因子：
30.5
通讯作者：
Jefferies WA
中科院分区：
文献类型：
--
作者：
Basha G;Omilusik K;Chavez-Steenbock A;Reinicke AT;Lack N;Choi KB;Jefferies WA
免疫应答由交叉呈递外源性抗原的树突状细胞（DC）启动和引发。CD74（不变链）分子伴侣蛋白被认为在MHC II类背景下专门促进DC引发。然而，我们在本文中证明了DC中的CD74依赖性MHC I类交叉呈递途径，其在产生针对病毒蛋白和细胞相关抗原的MHC I类限制性细胞溶解性T淋巴细胞（CTL）应答中起主要作用。CD74与树突状细胞内质网中的MHC I类分子结合，并介导MHC I类分子向内溶酶体区室的运输，以装载外源性肽。我们的结论是，CD74起着迄今为止，未发现的生理功能，内溶酶体DC交叉呈递引发MHC I类介导的CTL反应。
Immune responses are initiated and primed by dendritic cells (DCs) that cross-present exogenous antigen. The CD74 (invariant chain) chaperone protein is thought to exclusively promote DC priming in the context of MHC class II. However, we demonstrate herein a CD74-dependent MHC class I cross-presentation pathway in DCs that plays a major role in the generation of MHC class I restricted, cytolytic T lymphocyte (CTL) responses against viral protein- and cell-associated antigens. CD74 associates with MHC class I molecules in the endoplasmic reticulum of DCs and mediates trafficking of MHC class I to endolysosomal compartments for loading with exogenous peptides. We conclude that CD74 plays a hitherto, undiscovered physiological function in endolysosomal DC cross-presentation for priming MHC class I-mediated CTL responses.