SCIENTISTS FIND KEY TO IMMUNITY SYSTEM

Author: By Richard A. Knox Globe Staff

Date: Thursday, June 28, 1984
Page: ?????
Section: RUN OF PAPER

In a race with several groups around the world, Prof. Susumu Tonegawa and his colleagues at the Massachusetts Institute of Technology have been first to discover the complete structure of the so-called T-cell receptor and the genes that command its production. This two-pronged molecule sits on the surface of immune cells, called T-cells, and permits them to carry out their complex recognition-and-regulation mission.

Only three months ago, two other teams in Canada and California independently discovered the other half of the elusive T-cell receptor molecule.

The MIT discovery, reported today in the British journal Nature, is viewed by leading immunologists as a major breakthrough. They predict it will soon lead to a richer understanding of how immunity functions and how, in diseases as diverse as cancer and diabetes, it fails.

For several reasons, T-cells constitute the more important half of the immune system. They not only recognize infected cells and discriminate "self"
from "nonself," but they also regulate the activity of the other half, the antibody-producing cells called B-cells. The two cell types, which reside in the lymph system and circulate in the bloodstream, together make up every higher organism's defense against infection.

"The T-cell system is far more important than the B-cell system for the recognition of foreignness, and therefore for the impact (this finding* may have on health and disease," explained Prof. Baruj Benacceraf, president of the Dana Farber Cancer Center and a Nobel Prize-winning immunologist. "So this is a very important observation."

The number and variety of disease problems rooted in T-cell function is large. It includes viral, fungal and some bacterial infections; for instance, the reason that victims of Acquired Immune Deficiency Syndrome (AIDS) get overwhelming infections is that they have a deficiency of a subset of T-cells. It encompasses a wide variety of autoimmune disorders, such as arthritis and juvenile diabetes. Furthermore, many cancers are thought to arise because T- cells fail to recognize the malignant cells as "foreign."

In addition, the rejection of transplanted organs is a T-cell phenomenon. Therefore, a more selective way of preventing rejection could conceivably make it possible for a wide variety of tissues to be transplanted from any individual to any other.

Since 1974, scientists have made remarkable progress in discovering how B- cells can generate the enormous volume of unique antibodies - perhaps as many as a billion - that any organism might need to fight off invading bacteria, fungi and viruses during its lifetime.

In fact, Tonegawa made the key discoveries of how genes are rearranged within B-cells to assemble this vast variety of antibodies.

However, filling in the other half of the picture - how the T-cell is able to recognize both "self" and virtually any presenting foreign invader - has been a much more formidible task. Tonegawa explained in an interview this week that the basic difficulty was getting enough T-cells of a single type to do studies on.

A B-cell cranks out many millions of antibodies in response to a foreign protein, called an antigen. But the number of T-cells in an animal or human that bear a given receptor tailor-made to a particular antigen is very small. To complicate things further, the T-cell receptor generally can recognize a foreign antigen only when it is "presented" on the surface of a cell along with a "self" antigen, a molecule that marks every cell in an individual's body as unique.

Now that researchers have at last "got their hands on" the T-cell receptor and its genes, Tonegawa and others said, one of the next major tasks is to figure out how the T-cell accomplishes this "dual recognition" of self and foreign simultaneously.

KNOX ;06/27,15:24 KELLY;06/28,09: B07649445