医学免疫学第十一章：APC及抗原提呈(新)PPT.ppt

Endosomes Cell surface Uptake Class II associated invariant chain peptide (CLIP) (??inv)3 complexes directed towards endosomes by invariant chain Cathepsin L degrades Invariant chain CLIP blocks groove in MHC molecule MHC Class II containing vesicles fuse with antigen containing vesicles Removal of CLIP ? How can the peptide stably bind to a floppy binding site? Competition between large number of peptides HLA-DM catalyses the removal of CLIP MIIC compartment HLA-DM Replaces CLIP with a peptide antigen using a catalytic mechanism (i.e. efficient at sub-stoichiometric levels) Discovered using mutant cell lines that failed to present antigen HLA-DO may also play a role in peptide exchange Sequence in cytoplasmic tail retains HLA-DM in endosomes HLA-DM HLA-DR MIIC compartment sorts peptide-MHC complexes for surface expression or lysosomal degradation Surface expression of MHC class II- peptide complexes Exported to the cell surface (t1/2 = 50hr) Sent to lysosomes for degradation MHC-II Goes from Golgi (G) to MHC-II Compartment (MIIC) Where Peptide Loading Occurs Loading of MHC-II With Peptides From the Exterior Menu F B 溶 酶 体 途 径 外源性抗原 新合成的MHC-II类分子 （内质网中） 吞噬小体 li占据抗原结合槽 溶酶体 蛋白酶 MIIC 吞噬溶酶体 li CLIP 蛋白酶作用 DM 降解成13?18AA小肽 + CLIP脱落,暴露抗原结合槽 抗原肽/MHC II类分子复合物 转运至APC表面,供CD4+T细胞识别 吞噬、内吞、吞饮 Menu F B 概念 抗原提呈细胞 抗原提呈 -胞质溶胶途径 -溶酶体途径 -CD1分子提呈途径 主 要 内 容 CD1分子提呈途径 1. CD1的特征 分五型：CD1A、B、C、D、E, 与b2m组成二聚体； 与MHCI/II类分子有30%同源性，无多态性 CD1表达于专职APC表面，还可存在于内体/溶酶体腔室中，酸性环境改变其构象，与抗原结合 2. 抗原提呈特征 主要提呈糖脂或脂类抗原，特别是分支杆菌的某些成分 提呈给CD4+T、CD8+T、CD4-CD8-T、NK1.1T细胞 脂类抗原的CD1分子提呈途径 抗原提呈的三条途径 小 结 MPS的生物学功能。 成熟与未成熟DC的生物学特征及DC 的生物学功能。 试述胞质溶胶