Rolf M. Zinkernagel, M.D., Ph.D.

Rolf M. Zinkernagel

 Brief Bio

Rolf Martin Zinkernagel was born in Riehen, Switzerland, on January 6, 1944. After earning his M.D. from the University of Basel in 1970, he received a two-year postdoctoral fellowship in the Department of Biochemistry at the University of Lausanne. He began his training in immunology at Lausanne and learned first-hand the "frustrations of experimental lab work" while attempting to measure the radioactivity of cells infected by bacteria. In 1972, after taking a World Health Organization course on immunology taught by visiting professor Robert V. Blanden (AAI '77) at Lausanne, Zinkernagel applied for a second postdoctoral fellowship at the John Curtin School of Medical Research at Australian National University in Canberra, Australia, where he planned to study cell-mediated immunity to Listeria and Salmonella under Blanden. When Zinkernagel arrived in Canberra in January 1973, however, the only laboratory with available space was that occupied by another postdoctoral fellow—Peter Doherty. Shortly thereafter, Zinkernagel and Doherty began collaborating on the study of the immune response to LCMV, for which they were awarded the Nobel Prize.

Although Zinkernagel had not originally intended to pursue another degree when he moved to Australia, shortly after he began collaborating with Doherty, he entered the graduate immunology program at Australian National University, earning his Ph.D. in 1975. Recruited by Frank Dixon (AAI '50, president 1971–72), Zinkernagel accepted a position as an associate member of the Scripps Clinical Research Institute in La Jolla, California, in 1976. He also began teaching in the Department of Pathology at the University of California, San Diego. Shortly after being promoted to the rank of full member at Scripps in 1979, he returned to Switzerland to join the faculty of the Department of Pathology at the University of Zurich as associate professor. Promoted to full professor in 1988, Zinkernagel was appointed founding co-director of the university's Institute of Experimental Biology in 1992. He retired from both positions in 2008.

 Nobel Prize in Physiology or Medicine

1996 Nobel Prize in Physiology or Medicine with Peter C. Doherty (AAI '76) “for their discoveries concerning the specificity of the cell mediated immune defense.”

 Lasker Award

1995 Albert Lasker Basic Medical Research Award “for the landmark discovery of MHC restriction of T-cell recognition, and the altered-self hypothesis.” Click here for more details.

 AAI Service History

Joined: 1976

The Journal of Immunology
Associate Editor: 1978–1980

 Nobel Prize in Science

Rolf M. Zinkernagel, University of Zurich, was awarded the 1996 Nobel Prize for Physiology or Medicine jointly with Peter C. Doherty (AAI '76) for "their discoveries concerning the specificity of the cell mediated immune defense."

While examining immune reactions in mice infected with lymphocytic choriomeningitis virus (LCMV) from 1973 to 1974, Zinkernagel and Doherty found that virus-killing T lymphocytes taken from one mouse and injected into another could destroy infected cells only if the two mice belonged to the same strain. They discovered that T cells have to identify two kinds of molecules on the cell surface before they can actually recognize infected cells. One type of molecule is the viral antigen, and the other is a molecule from the major histocompatibility complex (MHC), a set of genes (and proteins) unique to each individual.

As early as the 1940s, researchers had noted variances in MHC proteins in cases where organ transplants were rejected, but the basis for the central role MHC played in determining the success of a transplant was not understood. Zinkernagel and Doherty uncovered the biological function of MHC proteins when they observed that these proteins served as a surveillance system to distinguish self from non-self. The strongest T cell responses were elicited by targets that were not completely foreign but were instead recognized as "altered self," consisting of a self-MHC protein attached to a non-self antigen.

This discovery fundamentally altered our understanding of how the immune system operates and has opened the way to advances in the areas of transplantation, vaccine development, and treatment of autoimmune and infectious diseases.

In subsequent work, Zinkernagel built upon his research with Doherty in his own laboratory. In the late 1970s, he elucidated the role of MHC in the thymus gland in selecting white blood cells for survival and maturation. More recently, he turned his attention to the co-evolution of viruses and their host immune systems.

"The whole field was in a mess" before Zinkernagel and Doherty's groundbreaking research of 1974, recalled Philippa Marrack (AAI '74, president 2000–01) of the National Jewish Center for Immunology and Respiratory Medicine in Denver (now National Jewish Health). "We were very confused about what T cells were up to. It wasn't until they made the observation that the T cell somehow has to recognize the two [signals] at the same time that the whole thing made sense."

Zinkernagel and Doherty had "changed everything, really," commented Philip D. Greenberg (AAI '82) of the University of Washington School of Medicine. Upon hearing that they had been awarded the Nobel, Greenberg said, "Most of us in the field felt this was an award that was coming and it was only a question of when they would get it."

 Awards and Honors

 Institutional/Biographical Links

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