Tuesday, July 31, 2007

Déjà vu in mice?

Neuroscientist Susumu Tonegawa at the Massachusetts Institute of Technology (MIT) has reported on a mechanism for déjà vu (French for “already seen”). We’ve all experienced it, that feeling that you’ve been somewhere, or seen something before, even though...

Wait a minute. I get a feeling I’ve already posted this piece.

I have.

But I also had a little bit of déjà vu when I first saw this article. I knew I’d seen that name before. It didn’t take me long to figure it out. Susumu Tonegawa won the Nobel Prize in 1987 for his work (in mice) on antibody diversity.

Tonegawa’s work had solved a problem that had perplexed scientists for years. Antibodies are proteins that attack invading germs (and other things) very specifically. An antibody can tell the difference between two very similar molecules. How can the body make antibodies that are so specific? If, as was thought at the time, each protein was coded by a different gene, it would require millions of genes just for making antibodies. There are only about 30,000 genes in the mouse.

The solution was elegant. Antibodies are made up of two kinds of proteins called heavy and light chains. Let’s just look at the heavy chain for now. Each heavy chain has a constant portion and a variable portion. It is the variable portion that binds to foreign substances. The gene for the heavy chain also has a constant portion, but the portion that encodes the variable portion is the part we’re interested in.

The variable portion can be divided into three parts, V, D, and J. There are hundreds of copies of the V part of the gene, each with a different sequence. There are 20 different D segments in humans (12 in the mouse) and 4 different J segments.

To make an antibody, you take one V segment, one D segment, and one J segment. That gives you tens of thousands of different combinations. The segments don’t always join up in the same way, adding more possibilities. Add to that different light chains with similarly arranged variable regions and there you have it—antibody diversity.