《抗原的加工與呈遞》ppt課件(文件)
【正文】 ? Biosynthesis and transportation of MHC classⅡ molecules – 粗面內(nèi)質(zhì)網(wǎng)中 MHCⅡ 類(lèi)分子合成 – 與 Ii鏈結(jié)合成 (αβIi )3復(fù)合物 Need to prevent newly synthesised, self proteins from binding to immature MHC Invariant chain stabilises MHC class II by binding to the immature MHC class II molecule In the Endoplasmic Reticulum MHC class II maturation and invariant chain Conception ? Ⅰ i鏈 – Ⅰ aassociated invariant chain， Ⅰ a分子相關(guān)的不變鏈 – 協(xié)助 Ⅱ 類(lèi)分子折疊和裝配 – 阻止 Ⅱ 類(lèi)分子與 ER中的新合成的肽或內(nèi)源性抗原肽結(jié)合 – 引導(dǎo) Ⅱ 類(lèi)分子進(jìn)入內(nèi)體 Structure of invariant chain Three extended peptides each bind into the grooves of three MHC class II molecules to form the nonomeric plex CLass II associated Invariant chain Peptide (CLIP) A peptide of the invariant chain blocks the MHC molecule binding site CLIP of invariant chain ? and b chains of MHC class II molecules CLIP Conception ? CLIP – Class Ⅱ associated invariant chain peptide ， Ⅱ 類(lèi)分子相關(guān)的不變鏈多肽 – Ⅰi 鏈中 81位至 104位氨基酸殘基的肽段結(jié)構(gòu) – 能與所有 MHCⅡ 類(lèi)分子抗原結(jié)合槽相結(jié)合 MHCⅡ 類(lèi)分子荷肽 ? Peptideloading of MHC class Ⅱ molecules – Ⅰi 鏈引導(dǎo)下 Ⅱ 類(lèi)分子進(jìn)入 內(nèi)體 (MⅡC ) – Ⅰi 鏈降解， Ⅱ 類(lèi)分子肽結(jié)合槽中保留 CLIP – HLADM催化， CLIP與肽結(jié)合槽解離 – HLADM編選，高親和力肽與 Ⅱ 類(lèi)分子結(jié)合 —— Ag肽 MHCⅡ 類(lèi)分子形成 Endosomes Cell surface Uptake Class II associated invariant chain peptide (CLIP) (?bIi)3 plexes 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 HLADM catalyses the removal of CLIP MIIC partment HLADM Replaces CLIP with a peptide antigen using a catalytic mechanism Sequence in cytoplasmic tail retains HLADM in endosomes HLADM HLADR Conception ? MⅡ C – MHC class Ⅱ partment， MHCⅡ 類(lèi)分子區(qū)室 – 富含外源性抗原肽、 MHCⅡ 類(lèi)分子、 HLADM的低 pH值的晚期內(nèi)體 – MHCⅡ 類(lèi)分子荷肽主要場(chǎng)所 ? HLADM的編選作用 – HLADM可驅(qū)逐與 Ⅱ 類(lèi)分子抗原結(jié)合槽低親和 力結(jié)
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