Thursday, April 17, 2008

Experimental Biology 2008, Part 3

  • There are three phases of cancer immunity: 1.) Elimination 2.) Equilibrium and 3.) Escape (meaning the tumor escapes from the immune system and grows and is detected). NKG2D and friends are involved with step 1, while adaptive immunity is involved with step 2.

  • Another talk I didn’t even have on my docket proved to be the star of the day. MICA is apparently very important to the process of a cell going from just a messed up little cell to a full-blown myeloma. It looks like when the cell figures out how to shed MICA it can progress to that worst stage. In fact, some myeloma drugs work by triggering the double-strand-DNA-break response and causing MICA to be put onto the cells. Anti-MICA monoclonal antibodies can vacuum up the soluble, shed MICA and help keep the myeloma in check.

  • In other news, sometimes tumors figure out how to retain MICA inside the ER so it can’t get out. This is an old virus trick – so tumors may be able to pick up on the tricks of those nasty little viruses.

  • You can make artificial Antigen Presenting Cells (APCs) with just 5-6 MHC-peptide complexes on them, plus some ICAM-1 and B7-1, and they can activate T cells for you. Could this work with MICA? What coreceptors would be needed?

  • I finally figured out what kind of therapy our lab’s super-MICA could be good for: DNA vaccination. A poster showed how DNA vaccination with the NKG2D ligands Rae-1 and H60 helped “helpless” T cells remember how to attack antigen (in this case, ovalbumin). This is perfect for our eventual super-duper-MICA, because it’s encoded in DNA and can be delivered through a DNA vaccine.

  • And, in the last talk I saw, I found out that a few years ago someone upended one of the points I make in biochemistry class. It turns out that in collagen, hydroxyproline is not really needed to interact with water and make the hydrophobic proline acceptable to water. Nope, it’s important because it’s an electron-withdrawing group that converts the mostly-cis Pro into mostly-trans hydroxyl-Pro: it helps set the right backbone configuration! The key is that F works as well as OH for stabilizing the molecule. So ... I guess I’ll have to change that slide ... can't I just use the same slides from year to year without them changing from underneath me??


Patrick said...

How does the vaccination of NKG2D ligands influence the response of "helpless (naive?)" T cells? I guess my immunology is a bit fuzzy.

BenMc said...

No, it is a bit weird. Many T cells express NKG2D as a co-receptor, so NKG2D ligands will co-activate them. The key word is co-! So this activation can make a T cell "remember" and stay "alert" a little better. Does that help a bit? It's the difference between being a killing activating receptor on NK cells and a co-receptor on T cells.