Wan Ying, Wu Yuzhang, Zhou Jingran, Zou Liyun, Liang Yunfei, Zhao Jianping, Jia Zhengcai, Engberg Jan, Bian Jiang, Zhou Wei
The Institute of Immunology, PLA, The Third Military Medical University, Shapingba District, Chongqing, PR China.
Eur J Immunol. 2005 Jul;35(7):2041-50. doi: 10.1002/eji.200425322.
It has been shown that exogenous antigens can access the MHC class I pathway of professional antigen-processing cells. However, details as to how the MHC class I-peptide complex forms in the presentation pathway are still poorly understood. Here we used MHC class I-peptide-specific antibodies to investigate the formation and intracellular location of class I-peptide complexes in macrophages. We observed that the formation of class I-peptide complexes occurs within a few hours and lasts for another few hours on the cell surface of macrophages following loading with filamentous phage particles. The class I-peptide complexes in the process were co-localized with MHC class II molecules and endocytic system markers. Moreover, endosomal compartments containing class I-peptide complexes were found within intracellular organelles stained by DiOC6 and calnexin. In addition, the cross-presentation of phage particles was transporter associated with antigen processing (TAP)-dependent and sensitive to proteasome inhibitors and NH(4)Cl. These data suggest that endocytosed phage particles may be processed and cross-presented in organelles positive for phagosome and endoplasmic reticulum (ER) markers via a classical ER MHC class I loading mechanism.
已表明外源性抗原可进入专职抗原加工细胞的MHC I类途径。然而，关于MHC I类 - 肽复合物在呈递途径中如何形成的细节仍知之甚少。在此，我们使用MHC I类 - 肽特异性抗体来研究巨噬细胞中I类 - 肽复合物的形成及其细胞内定位。我们观察到，在用丝状噬菌体颗粒加载后，I类 - 肽复合物在巨噬细胞的细胞表面在数小时内形成，并持续另外数小时。在此过程中的I类 - 肽复合物与MHC II类分子和内吞系统标志物共定位。此外，在由DiOC6和钙连蛋白染色的细胞内细胞器中发现了含有I类 - 肽复合物的内体区室。另外，噬菌体颗粒的交叉呈递是与抗原加工相关的转运体（TAP）依赖性的，并且对蛋白酶体抑制剂和NH(4)Cl敏感。这些数据表明，内吞的噬菌体颗粒可能通过经典的内质网MHC I类加载机制在对吞噬体和内质网（ER）标志物呈阳性的细胞器中进行加工和交叉呈递。
