Denzin MHC Flashcards
What does MHC class I activate? Class II?
Class I - activates CD8 - cytotoxic T lymphocyte
Class II - activates CD4 - T Helper Cells
What does MHC Class I present? MHC Class II?
I - presents peptides from proteins that were in the cell, usually from some sort of virus. Because it activates Cytotoxic T Lymphoctes, it will Kill that cell.
II - presented peptides that were endocytosed into the cell from outside. Usually it is bacteria or parasite.
Which cells Express MHC Class I? Class II?
I - all cells because all cells can be infected with a virus
II - only immune system cells because they are responsible for cleaning up the “outside world”
Structures of class I and Class II?
I - Heterodimer composed of alpha/alpha and alpha/beta micro globulin
II - composed of alpha/alpha and beta/beta
- both have a similar structure though of beta pleated sheets in the middle with alpha helices on the outside.
What is the size range that Class I can bind? Class II?
I - Can bind the smaller peptides. It is the bitten off hot dog. 7-10 AAs
II - can bind larger peptides. It is the full hot dog. 12-24 AAs
How does a peptides fit into the MHC molecule considering the immense amount of variability in peptides?
There is immense variability overall but only peptides that are the right length and have a certain type of AA in the right spot will bind to the MHC. These specific AAs in specific spots are called “anchors.” By the anchor there has to be a specific type of AA but elsewhere it can be whatever.
- works better for MHC I then MHC II
MHC Class I pathway
Basically when the virus gets in it begins to synthesize its own proteins. Once this happens, they begin to get ubiquinated and destroyed by the Proteasome. Once this happens, the peptides get brought to the ER where a transporter called TAP is waiting to bring the peptide into the ER. Then, ERAP trims the peptide so that it is the proper size to interact with the MHC Class I molecule. Tapasin acts kind of like a bridge to bring the TAP and MHC Class I into close proximity. Then the peptide interacts with MHC Class I in an endocytic vesicle and they are spit onto the cell membrane for CD8 to recognize.
TAP
Transporter that brings peptides into the ER during the MHC Class I pathway.
ERAP
Trims peptides in the ER down to the proper size to fit into the MHC Class I molecule during the MHC Class I pathway
Tapasin
Brings MHC Class I molecule in close contact with TAP so that it can get the peptides. It also ensures that only high affinity peptides are presented to MHC Class I molecule.
MHC Class II Pathway
Remember, Class II is specific for bacteria. So, what happens is that the APC (macrophage or dendritic cell) will ingest and kill the bacteria and use the protein as a signal to the CD4 cells. The way this works is that the protein antigen will be broken down by an endosome/lysosome. Then, separately, MHC Class II molecules are being prepared in the ER. Once the MHC Class II molecule is ready, it will go to the Golgi and then via a exocytic vesicle it will make its way to the endosome to interact with the peptides. Then once they come together they will be presented onto the surface of the cell. But wait, aren’t MHC Class I molecules in the ER and isn’t that where they interact with their antigens? Well to solve this problem we have something called an invariant chain (CLIP) that is bound to the MHC Class II molecule until it is the proper time to bind to the peptide in the endosome. The enzyme HLA-DM is involved in actively removing the CLIP molecule from MHC Class II.
Invariant chain
Binds to the MHC Class II molecule while in the ER so that the MHC Class II molecule doesn’t interact with all of the peptides in the ER. Then, once in the vesicle with the peptidies that were chopped up the invariant chain (CLIP) can be removed if something with a higher affinity can take its place.
HLA - DM
Removes CLIP from the groove of the MHC Class II molecule so that the MHC Class II molecule can interact with with the peptides in the vesicle.
What are the three types of professional APCs?
Macrophages
Dendritic cells
B cells
Dendritic Cells
These guys migrate through the tissues looking for bacteria. Eventually if they find it they will phagocytize it and they Will present the antigen when it gets to the lymph nodes. The lymph nodes are where all of the T cells live so it is able to present the antigen to the T cells.
- a good way to think of these guys is as photographers for a newspaper. They don’t do much other than report the news of the way and paint a recent picture of what’s going on. They have a short half-life because their pictures can get outdated.
