Ag加工和提呈.pptVIP

Degradation in the proteasome The components of the proteasome include MECL-1, LMP2, LMP7 These components are induced by IFN-? and replace constitutive components to confer proteolytic properties. LMP2 & 7 encoded in the MHC Proteasome cleaves proteins after hydrophobic and basic amino acids and releases peptides into the cytoplasm Cytoplasmic cellular proteins, including non-self proteins are degraded continuously by a multicatalytic protease of 28 subunits ENDOPLASMIC RETICULUM CYTOSOL Peptide antigens produced in the cytoplasm are physically separated from newly formed MHC class I Newly synthesised MHC class I molecules Peptides need access to the ER in order to be loaded onto MHC class I molecules ER membrane Lumen of ER Cytosol Transporters associated with antigen processing (TAP1 & 2) Transporter has preference for >8 amino acid peptides with hydrophobic C termini. TAP-1 TAP-2 Peptide TAP-1 TAP-2 Peptide TAP-1 TAP-2 Peptide TAP-1 TAP-2 Peptide TAP-1 TAP-2 Peptide TAP-1 TAP-2 Peptide TAP-1 TAP-2 Peptide TAP-1 TAP-2 Peptide TAP-1 TAP-2 Peptide TAP-1 TAP-2 Peptide ER membrane Lumen of ER Cytosol TAP-1 TAP-2 Peptide ATP-binding cassette (ABC) domain Hydrophobic transmembrane domain Peptide antigens from proteasome Endoplasmic reticulum Calnexin binds to nascent class I? chain until ?2-M binds TAP-1 TAP-2 Peptide TAP-1 TAP-2 Peptide TAP-1 TAP-2 Peptide TAP-1 TAP-2 Peptide TAP-1 TAP-2 Peptide TAP-1 TAP-2 Peptide TAP-1 TAP-2 Peptide TAP-1 TAP-2 Peptide TAP-1 TAP-2 Peptide TAP-1 TAP-2 Peptide TAP-1 TAP-2 Peptide B2-M binds and stabilises floppy MHC Tapasin, calreticulin, TAP 1 & 2 form a complex with the floppy MHC Cytoplasmic peptides are loaded onto the MHC molecule and the structure becomes compact Maturation and loading of MHC class I Fate of MHC class I Sent to lysosomes for degradation Exported to the cell surface MHCⅡ类途径的抗原加工和提呈 摄取抗原 吞噬小体 吞噬溶酶体 MHC-Ⅱ类分子 Ii链 复合体 MⅡC + 抗原肽MHC-Ⅱ类分子复合物 Ii链降解 CLIP Proteases produce ~24 amino acid long pept