AssessmentsMHC class I and MHC class II molecules
Content Reviewers:Rishi Desai, MD, MPH
Now, focusing on just T cells - they can only bind antigens, which are typically short peptides, when these antigens are displayed on a Major Histocompatibility Complex or MHC molecule which is sort of like a silver platter that is on the surface of a cell.
The MHC molecules are also called human leukocyte antigens and these proteins are encoded for by MHC genes, which are found on chromosome 6.
MHC class I genes encode the proteins HLA-A, HLA-B, and HLA-C, which is easy to remember as for MHC 1 it is always 1 letter.
MHC class II genes encode the proteins HLA-DP, DQ, and DR which is also easy to remember because for MHC class 2 there are always 2 letters.
And these genes are called histocompatibility because they are really important in determining whether or not a transplant is compatible or gets rejected.
But their role isn’t just to wreak havoc on transplants! They’re critically important in making sure that T cells recognize and react to antigens.
And even though they’re called human leukocyte antigens, they’re not just found in leukocytes or white blood cells.
In fact, the only cell that don’t have them are mature erythrocytes which don’t have a nucleus.
MHC class II molecules are only expressed on antigen presenting cells like monocytes, macrophages, dendritic cells, and B cells.
The MHC class I molecule has two protein chains, a larger alpha chain which contains both a peptide binding groove and a transmembrane region which anchors the MHC class I molecule onto the cell surface.
And there’s a beta-2-microglobulin chain which is linked to the alpha chain.
The alpha chain has three extracellular domains: alpha 1, alpha 2, and alpha 3.
Alpha 1 and Alpha 2 make up the peptide binding groove.
The beta-2-microglobulin basically props the whole structure up by binding between the alpha 1 & alpha 2 domains and the alpha 3 domain.
The peptide binding groove that binds peptides that are approximately 8-10 amino acids long with many hydrophobic residues that will bind easily to the hydrophilic amino acids inside the peptide binding groove of the MHC molecule.
MHC class I molecules allow immune cells to sample proteins from within your cells.
To do this, MHC class I molecules use what’s called the endogenous pathway of antigen presentation.
When a cellular protein is marked for degradation its sent to the an organelle called the proteasome - which is found in all nucleated cells.
The proteasome degrades the protein into short peptide chains, which are then transported to the endoplasmic reticulum using proteins called Transporters of Antigenic Peptides or TAP for short.