北大医学研究生课程-分子免疫学-MHC-医学课件.pptVIP

* ?蛋白酶体对内源性抗原的水解。 ?通过TAP复合物转运至内质网。 ?与MHC I类分子装配成复合物。 ?转运至高尔基体。 ?转运至细胞膜。 * Nascent class I MHC heavy chains and ?2-microglobulin are assembled with assistance from numerous chaperones (a). The MHC heterodimer is then recruited into the TAP-containing PLC via interactions with tapasin (b). Peptides generated by ubiquitin–proteasome-mediated protein turnover (c), some subsequently trimmed by cytosolic peptidases , are transported by TAP from the cytosol into the ER lumen (d). These peptides are bound by class I MHC, some after further trimming in the ER by ERAP, causing the fully folded class I MHC-peptide complexes to shed ER-associated chaperones (e). The peptide-MHC molecules migrate to the cell surface (f and g) where they are scanned by CD8+ T cells. * The class I assembly pathway and formation of peptide loading complex (PLC) Current Opinion in Immunology 2008, 20:75–81 * * A model of peptide transport begins with TAP in an inward/cytosol-facing conformation with the NBDs (nucleotide-binding domains) open. A peptide binds a cytosol-facing cavity formed by the TMDs (transmembrane domains), causing a conformational change that is transmitted to the NBDs. This conformational change permits ATP-dependent NBD closure, perhaps by facilitating exchange of ADP on TAP2 for ATP. As the NBDs close, the peptide-binding cavity closes to the cytosol and opens to the ER lumen, creating the closed, outward-facing conformation of TAP. Peptide affinity is markedly reduced in this conformation, and the peptide is hence released into the ER. ATP hydrolysis in the consensus ATPase site is sufficient to destabilize the closed NBDs (hydrolysis may also occur in the degenerate ATPase site, but this is not essential), which re-open to generate the resting conformation. Current Opinion in Immunology 2009, 21:84–91 * TAP1和TAP2（抗原处理相关的转运蛋白，transporter associated with antigen processing） 属于膜转运蛋白质