MHC Molecules




Antigens are molecules that induce a specific immune response. Often these are found on the surface of a bacterium or virus. Or sometimes they are free in solution.

But in two especially important circumstances, peptide antigens wind up bound to an MHC molecule on the surface of a cell of the body. In the first case, MHC I molecules bind peptides derived from proteins made in the cell itself. These then wind up "displayed" on the surface of the cell that made the protein. 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.




How does a peptide from a protein synthesized in a cell wind up bound to an MHC I molecule on the surface of the cell? These are the steps:




Do you recall the term for the type of molecule that specifically binds the peptide displayed on an MHC molecule?

Answer.



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:


Do you remember the term for the general type of molecule used by phagocytes to recognize a newly encountered foreign molecule? In other words, what is the general type of molecule used to recognize an antigen before a specific immune response has had a chance to make antibodies or T cell receptors?

ANSWER





MHC II Molecules and Dendritic Cells

Get Adobe Flash player 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.





Quick Quiz

Fill in Answer Correct False Correct Answer
What type of molecule on the surface of a cell displays peptides derived from proteins synthesized within the cell?
What secondary structure is characteristic of the extracellular domains of an MHC I molecule?
What widespread protein within a cell is bound to abnormal proteins targeted for destruction?
What structure moves peptides from proteins degraded at a proteasome into the endoplasmic reticulum?
What protein within a cell identifies abnormal proteins and attaches the above molecule that targets the protein for destruction?

(Spelling must be correct)
OK, Go ahead and give me: