人体免疫学课件-抗原的加工与递呈.pptVIP

Y Y Pinocytosis Phagocytosis Membrane Ig receptor mediated uptake Y Uptake of exogenous antigens Complement receptor mediated phagocytosis Y Fc receptor mediated phagocytosis Uptake mechanisms direct antigen into intracellular vesicles for exogenous antigen processing 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 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 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 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 MHC class II maturation and invariant chain 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 b chains of MHC class II molecules CLIP 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