MHC Molecules

In lecture, we have already encountered how MHC I molecules bind peptides derived from proteins made in the cell itself. These then wind up "displayed" on the surface of the cell. In addition, there are also MHC II molecules. By contrast, these bind and display peptides from protein that has been phagocytized. This page discusses both MHC I and MHC II molecules.

The purpose of peptides displayed on MHC molecules is to allow certain cells of the immune system to examine them via T cell receptors. This will be discussed much further in the near future.

MHC I Molecules

The basic structure of an MHC I molecule is shown by the diagram to the right. It is comprised of two polypeptide chains. The first is long and consists of an intracellular domain, a transmembrane domain, and three extracellular domains. The second polypeptide chain is short and consists of one domain.

The appearance of an MHC I molecule is shown to the left. Only the extracellular portions of the molecule are shown. Notice the peptide nestled in the top of the molecule. It is in this context that the TCR receptor binds its specific peptide antigen. (Green here corresponds to the red in the above figure.)

This next figure shows the same molecule in a ribbon format. Notice that the domains are based on beta sheets. In fact, these are homologous with the domains from which antibodies and T cell receptors are built. In addition, observe the alpha helices that create the groove in which the peptide is bound.

Here we see the same figure as above, except in TOP VIEW. Notice the groove in which the peptide lies, much like a hot dog in a bun.

At this point, review, if necessary, how a peptide from a protein synthesized in a cell winds up bound to an MHC I molecule on the surface of the cell. These are the steps:

• A protein (such as a viral protein) is marked for destruction by binding to ubiquitin
• The protein is degraded to peptides by a proteasome. For the MHC I molecule, the peptides are typically 9 amino acids in length (although they can vary from 8 to 11).
• The peptides are transferred into the rough ER via a TAP transporter.
• Meanwhile, an MHC I molecule is synthesized and placed in the membrane of the rough ER.
• A peptide binds in the groove in an MHC I molecule.
• The combination moves through the Golgi apparatus and into a secretion vesicle.
• Exocytosis of the secretion vesicle places the MHC I molecule with its peptide on the surface of the cell.
• The peptide and MHC I molecule are now in position to be recognized by a T cell receptor on a T cell.

MHC II Molecules

The MHC II molecule also has two polypeptide chains. But here each polypeptide chain consists of an intracellular domain, a transmembrane domain, and two extracellular domains. Nonetheless, a similar pocket for binding a peptide is found at the top. The domain structure is similar to the MHC I molecule.

The big difference, however, is that a peptide from a phagocytized protein is bound the the MHC II molecule on the surface of the cell. The sequence is:

• A pathogen is phagocytized, thereby winding up in a phagocytic vesicle.
• A lysosome with proteases fuses with the phagocytic vesicle, and the proteases digest the proteins into peptides.
• Meanwhile the MHC II molecule is synthesized in the rough ER.
• A vesicle with the MHC II molecule now fuses with the vesicle containing the peptides, and a peptide bind to each MHC II molecule.
• Exocytosis again places the MHC molecule and its peptide on the surface of the cell.
• The peptide and MHC II molecule are now in position to be recognized by a T cell receptor on a T cell.

MHC II Molecules and Dendritic Cells

Dendritic cells are a type of phagocytic cell that are distributed throughout the body. While phagocytosis is their key process, the phagocytosis is not primarily for the purpose of destroying microbes. Rather, the phagocytosis is used to capture antigens and transport them to lymphoid tissue in order to facilitate the development of an immune response.

In the lymphoid tissue, helper T cells check to see if their T cell receptors specifically bind the peptide displayed in the MHC II molecule.

Although phagocytic cells, certain dendritic cells also have a mechanism, which we won't investigate, for displaying peptides on MHC I molecules.