MHC class I and MHC class II molecules

MHC class I and MHC class II molecules


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High Yield Notes
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MHC class I and MHC class II molecules

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is loaded onto MHC class II molecule following release of the invariant chain in an acidified endosome.


Content Reviewers:

Rishi Desai, MD, MPH

Your immune system has an innate immune response which is immediate and nonspecific, as well as an adaptive immune response which is delayed and specific.

The adaptive immune is carried out by lots of unique B cells and T cells, which are highly specific for pathogens based on their unique parts - called antigens.

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.

There are actually two groups of genes. One group of genes encode the MHC class I molecule, which is bound by the CD8 molecule on the surface of cytotoxic T cells.

Another group of genes encode the MHC class II molecules which is bound by the CD4 molecule on the surface of helper T cells.

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.

HLA proteins that code for MHC class I molecules are found on all nucleated cells throughout the body, even platelets which are fragments of nucleated 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.