PathwayStep6635 PathwayStep6634 PathwayStep6637 PathwayStep6636 PathwayStep6632 PathwayStep6633 PathwayStep6630 PathwayStep6631 PathwayStep6629 PathwayStep6628 PathwayStep6627 PathwayStep6626 PathwayStep6625 PathwayStep6624 PathwayStep6623 PathwayStep6620 PathwayStep6621 PathwayStep6622 PathwayStep6615 PathwayStep6614 PathwayStep6617 PathwayStep6616 PathwayStep6619 PathwayStep6618 Recruitment of clathrin coated vesicle by Ii Internalization of MHC II:Ii clathrin coated vesicle Transport of MHC II:Ii complex to plasma membrane Insertion of MHC II:Ii complex in to the plasma membrane Initial proteolyis of Ii by aspartic proteases to lip22 Cleavage of lip22 to lip10 Uncoating of clathrin-coated vesicles and fusion with endosomes Trafficking of nonameric complex in the endocytic pathway Generation of CLIP from lip10 Disassociation of CLIP from MHC II MHC class II antigen internalization Reduction of disulphide bonds in MHC II antigens MHC class II antigen processing Loading of antigenic peptides Transport of antigen loaded MHC II molecules to surface Translocation of TGN-lysosome vesicle to lysosome TGN-lysosomal vesicle coat assembly TGN-lysosome vesicle uncoating and release of nonameric complex to lysosome Formation of COPII vesicle Formation of nonameric complex Translocation of MHC II:Ii complex to TGN Fusion of COPII vesicle with Golgi complex Interaction of invariant chain trimer and MHC II alpha beta dimer Formation of MHC II alpha beta heterodimer MHC class II antigen presentation Antigen presenting cells (APCs) such as B cells, dendritic cells (DCs) and monocytes/macrophages express major histocompatibility complex class II molecules (MHC II) at their surface and present exogenous antigenic peptides to CD4+ T helper cells. CD4+ T cells play a central role in immune protection. On their activation they stimulate differentiation of B cells into antibody-producing B-cell blasts and initiate adaptive immune responses. MHC class II molecules are transmembrane glycoprotein heterodimers of alpha and beta subunits. Newly synthesized MHC II molecules present in the endoplasmic reticulum bind to a chaperone protein called invariant (Ii) chain. The binding of Ii prevents the premature binding of self antigens to the nascent MHC molecules in the ER and also guides MHC molecules to endocytic compartments. In the acidic endosomal environment, Ii is degraded in a stepwise manner, ultimately to free the class II peptide-binding groove for loading of antigenic peptides. Exogenous antigens are internalized by the APC by receptor mediated endocytosis, phagocytosis or pinocytosis into endocytic compartments of MHC class II positive cells, where engulfed antigens are degraded in a low pH environment by multiple acidic proteases, generating MHC class II epitopes. Antigenic peptides are then loaded into the class II ligand-binding groove. The resulting class II peptide complexes then move to the cell surface, where they are scanned by CD4+ T cells for specific recognition (Berger & Roche 2009, Zhou & Blum 2004, Watts 2004, Landsverk et al. 2009). Authored: Garapati, P V, 2012-02-21 Edited: Garapati, P V, 2012-02-21 GENE ONTOLOGYGO:0019886 Pubmed11684289 Pubmed15224094 Pubmed15531770 Pubmed19092054 Pubmed19217269 Pubmed19703008 Pubmed8689559 Pubmed9316394 Reactome Database ID Release 432132295 Reactome, http://www.reactome.org ReactomeREACT_121399 Reviewed: Neefjes, Jacques, 2012-05-14