Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; email:
Joan and Sanford I. Weill Department of Medicine, Department of Microbiology and Immunology, and Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, Cornell University, New York, NY 10065, USA.
Annu Rev Immunol. 2018 Apr 26;36:717-753. doi: 10.1146/annurev-immunol-041015-055523. Epub 2018 Feb 28.
Antigen cross-presentation is an adaptation of the cellular process of loading MHC-I molecules with endogenous peptides during their biosynthesis within the endoplasmic reticulum. Cross-presented peptides derive from internalized proteins, microbial pathogens, and transformed or dying cells. The physical separation of internalized cargo from the endoplasmic reticulum, where the machinery for assembling peptide-MHC-I complexes resides, poses a challenge. To solve this problem, deliberate rewiring of organelle communication within cells is necessary to prepare for cross-presentation, and different endocytic receptors and vesicular traffic patterns customize the emergent cross-presentation compartment to the nature of the peptide source. Three distinct pathways of vesicular traffic converge to form the ideal cross-presentation compartment, each regulated differently to supply a unique component that enables cross-presentation of a diverse repertoire of peptides. Delivery of centerpiece MHC-I molecules is the critical step regulated by microbe-sensitive Toll-like receptors. Defining the subcellular sources of MHC-I and identifying sites of peptide loading during cross-presentation remain key challenges.
抗原交叉呈递是细胞内过程的一种适应性改变，即在内质网中合成 MHC-I 分子时，将内源性肽加载到 MHC-I 分子上。交叉呈递的肽来源于内化的蛋白质、微生物病原体、以及转化或死亡的细胞。内化货物与内质网的物理分离，而组装肽-MHC-I 复合物的机制就位于内质网中，这构成了一个挑战。为了解决这个问题，细胞内细胞器通讯的精心重布线是必要的，以准备交叉呈递，不同的内吞受体和囊泡运输模式将新兴的交叉呈递隔室定制为肽源的性质。三种不同的囊泡运输途径汇聚形成理想的交叉呈递隔室，每种途径的调节方式都不同，以提供独特的成分，从而能够交叉呈递多样化的肽库。中心 MHC-I 分子的递呈是受微生物敏感的 Toll 样受体调节的关键步骤。定义 MHC-I 的亚细胞来源并确定交叉呈递过程中肽加载的位点仍然是关键挑战。
