Mark M. Davis

The human genome contains about 25,000 genes, and yet the immune system’s T cells are capable of recognizing upwards of a billion different antigenic peptides. For years, scientists puzzled over how a small subset of the genome’s genes could produce the myriad T cell receptors needed to recognize every invading pathogen and cancer cell.

In 1980, fresh out of grad school, Mark Davis teamed up with a small group of scientists at the National Institutes of Health to solve the first part of that puzzle: they identified the gene for one of the two protein chains that make up the T cell receptor. A few years later, after setting up his own lab at Stanford University, Davis and his colleagues pinned down the gene for the second protein chain. They also showed that variable regions within each of these genes produce the diversity needed by T cell receptors to bind an array of peptides.

Since these initial studies, Davis and his research group have pieced together many other details of T cell and antigen interactions. For example, they demonstrated that T cells can recognize single molecules of antigen, and that even fleeting interactions with antigen-presenting cells are sufficient to activate T cells.

More recently, Davis, who became an HHMI investigator in 1987, has begun investigating the human immune system as a whole. In one study, he analyzed more than 200 variables in the immune systems of twins, and found that most variation – including the flu vaccine response – was driven by nonheritable influences that were most likely environmental. He’s also been comparing the immune systems of children in Palo Alto, California with children of the same age in Bangladesh, hoping to gain a better understanding of how environmental factors, such as microbes, shape the immune system.

Image: Tony Avelar

About the HHMI Investigator Program

HHMI investigators, appointed through rigorous competitions, are among the most creative and promising biomedical researchers in the United States. The scientists receive long-term, flexible support, enabling them to follow their own curiosity in the pursuit of significant biological questions. The Investigator Program is the Institute’s flagship program, with an annual commitment of more than $600 million to support the investigators and their host institutions across the country. The collaboration between HHMI and these institutions powerfully extends the nation’s research capacity. Read more >>