MHC & Peptide Processing
Internal MHC I
A small percentage of all the proteins inside the Cytosol of a cell are degraded by a Low Molecular Weight Protease (LMP).
They are then, moved from the CytoPlasm to the Rough Endoplasmic Reticulum(RER), by the Transporter of Antigenic Peptide (TAP) protein.
Inside the RER some of these Peptides, which are approximately ten Amino Acids in length, will associate with the alpha-1 and alpha-2 proteins of MHC Class I.
The Peptide must bind to the cleft, between the alpha-1 and alpha-2 domains of the molecule, and produce a change in shape.
This allows for the association of the beta-2 MicroGlobulin, or the MHC molecule will destabilize and not be expressed on the cell surface.
Peptides which meet this requirement form a complex with the MHC Class I molecule. This complex is transported in a Vesicle from the RER to the Golgi Body and from there to the surface of the cell.
With the exception of Neurons, all Somatic Nucleated Cells express MHC Class I on their surfaces.
Exogenous MHC II
The MHC Class II molecule primarily presents Peptides, which have been digested from external sources.
Since only Antigen Presenting Cells (APCs) digest foreign protein, these are the only cells which normally express MHC II on their surface.
The path toward the surface of a cell is somewhat different for a Class II molecule.
Within the RER the alpha and beta proteins of the molecule, associate with each other, and a third protein called the "invariant chain," which stabilizes the complex.
In the absence of the invariant chain, the alpha and beta proteins will not associate. The MHC-invariant complex is then passed from the RER, into and out of, the Golgi body.
Before it proceeds to the surface of the cell, the vesicle which contains the complex, fuses with an Endocytic compartment, where an external protein has been sampled and degraded.
In this compartment, the invariant chain is destroyed and part of the degraded protein associates with the MHC II molecule, in the cleft between the alpha-1 and beta-1 domains.
The resulting MHC II-Peptide complex, proceeds to the surface where it is expressed. MHC II molecules are expressed on the surface of cells in pairs.
Exogenous MHC I
Though the exact mechanism has yet to be determined, it is possible for certain APCs to ingest and degrade proteins, and associate them with MHC I molecules.
This pathway is of particular interest for the developers of vaccines, who wish to induce a T-Cell response by inoculation with Exogenous Peptides.