医学免疫学课件APC及抗原提呈－2015.ppt

* * The peptide/MHCII complexes are transported to sell surface and its half life time is 50hr. The other MHC II molecules including MHCII with CLIP, the empty MHCII and misfolded MHCII molecules are sent to lysosomes for degradation. * Figure 5.9. This is endoplasmic reticulum where the new proteins are synthesized. Here we can see the new synthesized MHC II molecule. This polypeptide chain is called invariant chain (li) which forms a complex with MHC II, blocking the binding of peptides and misfolded proteins. HLA-DM facilitates the loading of antigenic peptides onto class II molecules. The invariant chain binds to newly synthesized MHC class II molecules and blocks the binding of peptides and unfolded proteins in the endoplasmic reticulum and during the transport of the MHC class II molecule into acidified endocytic vesicles (first panel). In such vesicles, proteases cleave the invariant chain, leaving the CLIP peptide bound to the MHC class II molecule (second panel). Pathogens and their proteins are broken down into peptides within acidified endocytic vesicles, but these peptides cannot bind to MHC class II molecules that are occupied by CLIP (third panel). The class II-like molecule, HLA-DM, binds to MHC class II:CLIP complexes, catalyzing the release of CLIP and the binding of antigenic peptides (fourth panel). * 新合成的MHCII在内质网与li结合, li为三聚体,每一个亚单位与一个分子的MHCII抗原结合槽结合,形成九链聚合体.其功能有两个: (1) 防止无关肽与MHCII结合; (2) 引导MHCII离开内质网, 运至含有特异性肽的内体. 当MHCII小泡与内体融合, 酸性环境下,蛋白酶将li降解, 仅留CLIP(class II -associated invariant-chain peptide，II类相关恒定链肽)仍结合在抗原结合槽内. HLA-DM可促进CLIP从抗原槽内解离, 并促进抗原肽结合进去。 左图：外源性抗原通过MHC-I类分子交叉递呈：外源性抗原通过受体内化，被部分降解，进而被允许转位至胞质，由蛋白酶体降解；或抗原直接从吞噬溶酶体转位至另一小室，与成熟MHC-I类分子结合。 右图：内源性抗原通过MHC-II类分子交叉递呈：细胞将自身胞浆蛋白摄入自噬体，后者与溶酶体融合，将内源性蛋白降解成肽，通过MHC-II类分子递呈。 * * Exogenous antigen: antigen can be taken up by APC from extracellular fluid. Endogenous antigen: antigen are synthesized by APC and exist in the cytosol. Virus can live in the host cell and use materials from host cells to synt