MHC class II antigen presentation

Stable Identifier
Homo sapiens
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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).
Literature References
PubMed ID Title Journal Year
8689559 How MHC class II molecules acquire peptide cargo: biosynthesis and trafficking through the endocytic pathway

Ploegh, HL, Wolf, PR

Annu Rev Cell Dev Biol 1995
9316394 Peptide binding and antigen presentation by class II histocompatibility glycoproteins

Jensen, PE

Biopolymers 1997
11684289 Presentation of antigens by MHC class II molecules: getting the most out of them

Villadangos, JA

Mol Immunol 2001
19703008 MHC II and the endocytic pathway: regulation by invariant chain

Landsverk, OJ, Gregers, TF, Bakke, O

Scand J Immunol 2009
19217269 MHC molecules and microbial antigen processing in phagosomes

Simmons, D, Harding, CV, Ramachandra, L

Curr Opin Immunol 2009
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