免疫学抗原递呈细胞和抗原讲义.ppt

Y Y Pinocytosis Phagocytosis 膜Ig受体介导摄取 Y 外源抗原的摄取 Complement receptor mediated phagocytosis 补体受体介导的吞噬作用 Y Fc receptor mediated phagocytosis Fc受体介导的吞噬作用 摄取作用介导外源抗源进入细胞内形成内体，以便加工 吞噬作用 胞饮作用 100 50 75 25 0 % of max. T cell response 10-1 10-2 10-3 Antigen ?gml-1 Receptor-mediated antigen uptake Non-receptor -mediated uptake Receptor-mediated uptake enhances the efficiency of the T cell response 2. 外源性抗原的加工 外源性抗原在内体的酸性环境和蛋白酶的作用下被降解成适于与MHCⅡ类分子结合的肽。 Proteases produce ~24 amino acid long peptides from antigens Drugs that raise the pH of endosomes inhibit antigen processing Endosomes Exogenous pathway Increase in acidity Cell surface To lysosomes Uptake Protein antigens In endosome Cathepsin B, D and L proteases are activated by the decrease in pH 组织蛋白酶 Activation of Cathepsin B at low pH At higher pH cathepsin B exists in a pro-enzyme form Acidification of the endosome alters the conformation of the proenzyme to allow cleavage of the pro-region Loss of the pro-region exposes the catalytic site of the protease Hence: drugs that alter acidification of the endosomes disturb exogenous antigen processing 3. MHC Ⅱ类分子的生物合成和转运 在粗面内质网合成，α/β二聚体与Ii链结合。 Ii链：Ia-associated invariant chain, Ii链 CLIP：Ii链中81-104位氨基酸残基的特殊肽段结构，能与所有MHCⅡ类分子的抗原结合槽以不同亲和力结合，称为Ⅱ类分子结合的不变肽链（class II associated invariant peptide, CLIP) Ii链的作用： 帮助II类分子折叠和装配 阻止II类分子与ER中新合成的肽或内源性抗原肽结合 引导II类分子进入内体 Need to prevent newly synthesised, unfolded self proteins from binding to immature MHC Invariant chain stabilises MHC class II by non- covalently binding to the immature MHC class II molecule and forming a nonomeric complex In the endoplasmic reticulum-内质网 MHC class II maturation and invariant chain 成熟与不变链 Invariant chain structure Three extended peptides each bind into the grooves of three MHC class II molecules to form the nonomeric complex A peptide of the invariant chain blocks the MHC molecule binding site. This peptide is called the CLass II associated Invariant chain Peptide (CLIP) Invariant chain CLIP peptide and