My goal in this post is to make immunology seem fascinating (because if I can science, so can you).
I’ll be summarizing the MHC class I antigen presentation pathway, which I happen to find pretty neat. I’ve tried to simplify things so that anyone can follow along, but without sacrificing the more interesting details. If any of you immunologists out there catch an error, let me know.
So here’s the big picture:
John Doe has a raging viral infection. He’s got loads of virus particles floating around in his ECF, and his humoral immune response is doing a decent job of neutralizing these viruses and slowing down the infection.
But there’s still a problem. The virus has infected a number of John Doe’s own cells…and until his immune system can eliminate these infected cells, they’re just going to keep pumping out hordes of new viruses (infecting even more cells).
Basically, John’s immune system needs to figure out a way to destroy his own infected cells…preferably without killing his healthy cells.
And now, the smaller picture:
Inside the infected “John-cell”, the virus has commandeered John’s own cellular machinery to replicate itself. The cytoplasm is filling up with viral proteins, which will then assemble into new viruses and march forth from the John-cell to pillage and plunder the surrounding countryside. (There’s a joke about “orcs and immuno-goblins” there somewhere.)
In a previous post, I explained how proteasomes work to degrade proteins and recycle their components. Now John’s proteasomes are once again on the scene.
Since the proteasomes are doing their normal job – floating around in the cytoplasm and chopping up unwanted proteins – they naturally end up destroying some of these viral proteins. The viral proteins are cleaved into peptide fragments, generally 4-20 amino acids in length.
In the meantime, TAP-transporters, located on the endoplasmic reticulum, are selectively moving peptides (mostly 6-15 amino acids in length) from the cytoplasm into the ER lumen. With the assistance of a protein called tapasin, these viral peptide fragments are bound to MHC class I molecules.
These peptide-bound MHC class I molecules (mouthful, right?) are then transported, via the Golgi, to the cell membrane. The MHC molecules sit on the surface of the cell and present their antigens (the viral protein fragment, in this case).
John’s immune system uses CD8+ cytotoxic T cells to “police” John’s own cells. When they recognize a cell presenting foreign antigens (“Nah man, we don’t use THAT combination of amino acids in OUR proteins!”) they attach to the infected cell and destroy it.
So that’s pretty much how MHC class I antigen processing & presentation works. I bet you can’t wait to tell all your friends.