| Themes > Science > Life Sciences > General Biology > Immunology > Recognition Systems in Immunity > The Major Histocompatibility Complex > Two pathways for antigen processing |
The 2 classes of MHC molecule are specialised to present different sources of antigen. MHC class I molecules present endogenously synthesised antigens, e.g. viral proteins. MHC class II molecules present exogenously derived proteins, e.g. bacterial products or viral capsid proteins. The cell biology and expression patterns of each class of MHC are tailored to meet these distinct roles. MHC class I molecules are very unstable in the absence of peptide. They bind peptides in the Endoplasmic reticulum (ER). Peptides are generated continuously in the cytoplasm by the degradation of proteins, predominantly by the proteasome. Peptides of suitable length (~8-18 amino acids) are specifically transported across the ER membrane by a heterodimeric transporter made up of the TAP1 and TAP2 molecules. These peptides bind to the class I MHC molecules in the ER if they have appropriate sequence motifs, the MHC molecules being stabilised in a partially folded state by a chaperone protein (p88, calnexin). The peptide bound class I MHC molecules adopt their fully folded conformation, release calnexin and transit to the cell surface via the golgi. Click here to see a
diagram of the Class I antigen processing pathway MHC class II molecules bind to a third polypeptide in the ER called invariant chain or Ii. The invariant chain serves two purposes. It blocks the binding of peptides to the class II molecule and it targets the class II molecule to a specialised endosomal compartment (MIIC). Exogenous antigens enter the cell in membrane vesicles, either by fluid phase pincytosis or receptor mediated endocytosis. These vesicles fuse with the MIIC compartment. The MIIC compartment has an acid pH and contains proteases, this combination unfolds and degrades both the antigen and the invariant chain causing the generation of antigenic peptides and the release of class II molecules to bind those peptides with appropriate sequence motifs. The class II molecules, peptide complexed or "empty", then traffic to the plasma membrane. Click here to see a diagram of the Class II antigen processing pathway |
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