ZINKERNAGEL, ROLF M.

born Jan. 6, 1944, Basel, Switz. Swiss immunologist and pathologist who, along with Peter C. Doherty of Australia, received the Nobel Prize for Physiology or Medicine in 1996 for their discovery of how the immune system distinguishes virus-infected cells from normal cells. Zinkernagel received his M.D. from the University of Basel in 1970 and his Ph.D. from the Australian National University, Canberra, in 1975. He joined the John Curtin School of Medical Research in Canberra in 1973 as a research fellow and soon began collaborating with Doherty on a study of the role the immune system plays in protecting mice against infection by the lymphocytic choriomeningitis virus, which can cause meningitis. Their research centred on the white blood cells known as cytotoxic T lymphocytes, which act to destroy invading viruses and virus-infected cells. In their experiments, Zinkernagel and Doherty found that T lymphocytes from an infected mouse would destroy virus-infected cells from another mouse only if both mice belonged to a genetically identical strain. The T lymphocytes would ignore virus-infected cells taken from a different strain of laboratory mice. Further research showed that in order to kill infected cells, T lymphocytes must recognize two major signals on the surface of an infected cell: those of the infecting virus and certain self molecules called major histocompatibility complex (MHC) antigens, which tell the immune system that a particular cell belongs to one's own body. In the experiment, the T lymphocytes from one mouse strain could not recognize MHC antigens from another on the infected cells, so no immune response occurred. The discovery that T lymphocytes must simultaneously recognize both self and foreign molecules on a cell in order to react against it formed the basis for a new understanding of the general mechanisms of cellular immunity. After leaving the Curtin School in 1975, Zinkernagel served as an associate professor (197988) and full professor (198892) at the University of Zrich and became head of the university's Institute of Experimental Immunology in 1992.