青岛大学：基础医学院（PPT课件讲稿）外源性抗原提呈途径（MHC II分子相关的外源性抗原的提呈途径 Pathway of MHC class II associated exogenous antigen presentation）

MHCII分子相关的外源性抗原的提呈途径(Pathwayof MHCclassIIassociatedexogenous antigen presentation

MHC II分子相关的外源性抗原的提呈途径 （Pathway of MHC class II associated exogenous antigen presentation ）

Pathway of MHC class II associated细antigenpresentation香睡缓推摄取伪是善唯体安一容酶体客游体饰绿雨8exogenous antigen香唯滨精体1→>are taken up by APCsX吞噬细胞的吞噬杀伤过程示意图→processed intopeptides→ that bind to MHC II moleculesforming peptide/ MHC II complex→ transported to the cell surface→presented to CD4+Tcell

Pathway of MHC class II associated antigen presentation exogenous antigen → are taken up by APCs → processed into peptides → that bind to MHC II molecules forming peptide/ MHC II complex → transported to the cell surface → presented to CD4+T cell

Stages of exogenous antigen processingUPTAKEAccess of native antigens and pathogens tointracellular pathways of degradation

Stages of exogenous antigen processing 1. UPTAKE Access of native antigens and pathogens to intracellular pathways of degradation

VptakeofexogenousantigensMembraneIgreceptormediatedendocytosisPhagocytosisComplementreceptormediatedendocytosisinocytosisopsonizationFcreceptormediatedendocytosisVptake mechanisms direct antigen into intracellularvesiclesforexogenousantigenprocessing

Y Pinocytosis Phagocytosis Membrane Ig receptor mediated endocytosis Y Uptake of exogenous antigens Complement receptor mediated endocytosis Fc receptor mediated endocytosis opsonization Uptake mechanisms direct antigen into intracellular vesicles for exogenous antigen processing

2.DEGRADATIONProteolysis of antigens to peptides

2. DEGRADATION Proteolysis of antigens to peptides

Cell surfaceProteinantigensUptakeInendosomeEndosomesIncreaseinacidityTolysosomesProteasesareactivatedbythedecreaseinpHProteasesproduce~24aminoacidlongpeptidesfromantigensDrugsthat raisethepHofendosomesinhibitantigenprocessing

Proteases produce ~24 amino acid long peptides from antigens Drugs that raise the pH of endosomes inhibit antigen processing Endosomes Increase in acidity Cell surface To lysosomes Uptake Protein antigens In endosome Proteases are activated by the decrease in pH

3. PEPTIDE-MHC II COMPLEX FORMATIONLoading of peptides onto MHCII molecules

3. PEPTIDE-MHC II COMPLEX FORMATION Loading of peptides onto MHC II molecules

MHC class II maturation and invariant chainIntheendoplasmicreticulumMHCII类分子MHCI类分子肽结合区免疫球蛋S白样区βCTm+c跨膜区胞浆区MHCI类分子和II类分子及其编码基因的结构InvariantchainstabilizesMHCclasslibynon-covalentlybindingtotheimmatureMHcclassllmoleculeandforminganonamericcomplex

Invariant chain stabilizes MHC class II by non- covalently binding to the immature MHC class II molecule and forming a nonameric complex In the endoplasmic reticulum MHC class II maturation and invariant chain  

The functions of invariant chain- promote the right folding of MHCII- block MHC unspecific binding topeptides- direct MHC from ER to endosomesFurther cleavage leavesa shortliiscleaved initiallyto leaveaInvariantchain(li)bindsinpeptidefragment,CLiP,boundthegroove ofMHC class Ilfragmentboundtotheclass ltotheclass ll moleculemoleculeandtothemembranemoleculeThreeextended peptideseachbind into thegroovesof three MHC class Ilmoleculestoformthenonamericcomplex

The functions of invariant chain - promote the right folding of MHCII - block MHC unspecific binding to peptides - direct MHC from ER to endosomes Three extended peptides each bind into the grooves of three MHC class II molecules to form the nonameric complex. CLIP: CLass II associated Invariant chain Peptide

Class II associated invariant chain peptide (CLIPCell surfaceEndosomesUptakeMHC ClassII(αβinv)3complexesCathepsinLdegradesInvariantchaindirectedtowardscontaining vesiclesCLIPblocksgrooveinMHCendosomesbyfuse with antigeninvariantchainmoleculecontaining vesicles

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 molecule MHC Class II containing vesicles fuse with antigen containing vesicles