posted by: Issa Abu-Dayyeh
Every couple of months I ultimately get into a discussion about the role of MHC class I and II in the activation of immune functions. What drives their transcription/translation, what cells produce them, how are the peptides found and loaded on them; these are many questions that do not seem to go in the long-term memory section of my brain as well as many others.
Here I decided -once and for all- to summarize the dogmas in the aspects mentioned previously.
MHC class I are molecules produced by all nucleated cells, their production is augmented by IFN-alpha, IFN-beta, IFN-gamma, and TNF-alpha. They are loaded with peptides that result from proteasome-mediated degradation of proteins found in the cytosol, they are transported to be expressed on the surface of cells, and MHC I molecules bound to foreign peptides activate CD8+ T cells by binding to their TCR.
In other words, these MHC molecules keep the internal contents of molecules in check. This is consistent with the fact that such a mechanism is very useful against cancer cells and cells infected with viruses that are actively producing their proteins inside the cells.
On the other hand, MHC class II molecules are produced by antigen presenting cells of the immune system: mainly dendritic cells, macrophages, and B cells. Their production is primarily driven by IFN-gamma (and not the other interferons), they are loaded with peptides that are generated by peptidases found inside phagolysosomes, and upon their translocation to the cell surface, they activate CD4+ T cells.
Two main comments come to my mind upon writing those “facts”:
1- It is impressive how those two MHC types seem to complement each other’s function. MHC I screens for internal “problems”: viruses, cancer, and other antigens that are hiding inside cells away from immune detection, while MHC class II are directed against obvious intruders that go inside the cells by phagocytosis (or any surface detection mechanism ex: TLR) such as: bacteria and parasites. Together, those two molecules work hand in hand in keeping the organism as alert as possible to all sorts of invaders.
2-Although it is interesting per se that interferons and other pro-inflammatory cytokines upregulate the production of those molecules, it is even more interesting to see that molecules such as IFN-gamma which is not typically involved in counter-acting viral infections can upregulate MHC type I molecules. To me, this suggests that an invasion of the immune system by viruses must somehow lead to the production of danger signals recognized by IFN-gamma producing cells (or their activators) and ultimately leads to a response against those viruses through MHC I upregulation (Future work in the field will be the judge!)
In the end, it is as if the immune system is on “code red” and asks each cell to rapidly disply its ID card to the immune police….Normal cells will show the good ID and pass, suspicious cells will display a “wanted” ID and are destined to be eliminated.
Isn’t it amaizing???