Two genes critical to the immune system's adaptability in battling viruses, bacteria and other invaders receive on and off signals from a single DNA segment, HHMI researchers have found. The discovery explains how the two genes work in concert and hints at how the genes have managed to remain partners for more than 450 million years since they first appeared in cartilagenous fish as part of an adaptive immune system.
In an article in the August 13, 1999, issue of the journal Science, HHMI investigator Michel Nussenzweig and colleagues at The Rockefeller University reported that neighboring genes, called RAG1 and RAG2, are switched on in concert by a single genetic control signal nestled near RAG2 on the chromosome. The discovery is like finding that a light switch in one house also controls lights in a house across the street.
The RAG1 and RAG2 genes produce proteins that somehow join to form a "transposase," an enzyme that helps snip apart and rearrange genes that code for two critical weapons in the immune system's arsenal. These weapons are protein antibodies produced by the immune system's B cells and receptors found on the surface of T cells.
Antibodies are molecules that roam the bloodstream, recognizing and attaching to invaders and marking them for destruction. Similarly, the receptors on T cells-- the immune system's infection-fighting "soldiers"-- are those that recognize antigens, fragments of foreign proteins, so that the T cells can attack the viral or bacterial proteins.
The RAG1/RAG2 recombinases' ability to rearrange the genes for such
antibodies and receptors is crucial to the immune system's flexibility in
generating a nearly infinite variety of weapons against infections and malignant
cells. HHMI investigator David Shatz discovered RAG1 and RAG2 in 1989 and in
1998 with colleagues at Yale University, he showed
Contact: Jim keeley
Howard Hughes Medical Institute