Second T cell receptor found.

Second T cell receptor found

In the complex orchestra of the immune system there are instruments whose roles are unknown, and there are sounds with no known source. One instrument emerged from behind the curtains at last week's 6th International Congress of Immunology in Toronto. While it generated quite a bit of excitement at the meeting, researchers do not yet know whether it plays a minor or major role in the immune system.

The newly discovered instrument is a protein molecule on the surface of T cells. One of the two major arms of the immune system, T cells are primarily involved in ridding the body of foreign organisms -- fungi, parasites, cancer cells, foreign tissue and virally infected cells. Each T cell recognizes and works against one subtype within these groups, through a specific receptor on its cell membrane.

At the Toronto meeting, Michael B. Brenner of Harvard University and Leonard Chess of Columbia University in New York City presented research by their laboratories indicating that there is a second class of T cell receptors. The experiments are also described in the July 10 NATURE.

The second receptor, says Brenner, is "a cousin but clearly distinct" from the first. While it opens up a whole new area of investigation for immunologists -- detailing the function of the receptor and its role in disease -- Brenner and Chess say it is too early to predict the clinical applications of the finding.

The second receptor had been hotly pursued following the discovery of a "mystery gene" by Haruo Saito and Susumu Tonegawa at the Massachusetts Institute of Technology in Cambridge in 1984. Unlike the two genes that together code the first receptor, this gene is active in T cells at the time of their development. Like the first two genes, it can create many different proteins by rearranging itself. Prior to last week's announcement, the gene's function was unknown. Now that the product of the gene has been found, researchers are seeking the protein's "sound."

Brenner's and Chess's laboratories took different routes to their discoveries. Since the MIT work suggested the gene was active early in T cell development, and since the other T cell receptor appears relatively late, Chess's group worked with clones of immature cells. They looked for an intermediate step in protein production based on the genetic sequence of the mystery gene and found what they were looking for.

Brenner's laboratory used monoclonal antibodies on a preparation of T cells to "cleanse" it of the known receptor; they found a novel protein on the remaining cells that matched up with predictions of what the mystery gene would produce. In both cases, the new receptor was found in conjunction with another cell-surface molecule that the other receptor requires in order to be viable, indicating that the new receptor may have a similar recognition function.

"It used to be you started with a phenomenon, looked for a protein, then looked for the gene," says Chess. Having taken the reverse route in this case, the researchers now need to determine exactly what the protein does. "We have to know more about its function before we can say anything about its effect. We're hoping it will have some impact on our understanding of the immune system," says Chess.

Says Philip Halloran, an organ transplant specialist at Mt. Sinai Hospital in Toronto, "This is a new window on how T cells work. How important it will be depends on what we can see through the window."