The Nobel Prize in Physiology or Medicine 1996

The Nobel Prize in Physiology or Medicine 1996 was awarded jointly to Peter C. Doherty and Rolf M. Zinkernagel “for their discoveries concerning the specificity of the cell mediated immune defence.”

Nobelist Born Affiliation at the time of the award
Peter C. Doherty 15 October 1940, Brisbane, Australia St. Jude Children’s Research Hospital, Memphis, TN, USA
Rolf M. Zinkernagel 6 January 1944, Basel, Switzerland University of Zurich, Institute of Experimental Immunology, Zurich, Switzerland


Peter Doherty and Rolf Zinkernagel have been awarded this year’s Nobel Prize in Physiology or Medicine for the discovery of how the immune system recognizes virus-infected cells. Their discovery has, in its turn, laid a foundation for an understanding of general mechanisms used by the cellular immune system to recognize both foreign microorganisms and self molecules. This discovery is therefore highly relevant to clinical medicine. It relates both to efforts to strengthen the immune response against invading microorganisms and certain forms of cancer, and to efforts to diminish the effects of autoimmune reactions in inflammatory diseases, such as rheumatic conditions, multiple sclerosis and diabetes.

The two Nobel Laureates carried out the research for which they have now been awarded the Prize in 1973-75 at the John Curtin School of Medical Research in Canberra, Australia, where Peter Doherty already held his position and to which Rolf Zinkernagel came from Switzerland as a research fellow. During their studies of the response of mice to viruses, they found that white blood cells (lymphocytes) must recognize both the virus and certain self molecules – the so-called major histocompatibility antigens – in order to kill the virus-infected cells. This principle of simultaneous recognition of both self and foreign molecules has since then constituted a foundation for the further understanding of the specificity of the cellular immune system.

The immune system consists of different kinds of white blood cells, including T- and B- lymphocytes whose common function is to protect the individual against infections by means of eliminating invading microorganisms and infected cells. At the same time they must avoid damaging the own organism. What is required is a well developed recognition system that enables lymphocytes to distinguish between on the one hand microorganisms and infected cells, and on the other, the individual´s normal cells. In addition, the recognition system must be able to determine when white blood cells with a capacity to kill should be activated.

In the early 1970s when Peter Doherty and Rolf Zinkernagel had begun their scientific work within immunology, it was possible to distinguish between antibody-mediated and cell- mediated immunity. It was known that antibodies that are produced by B-lymphocytes are able to recognize and eliminate certain microorganisms, particularly bacteria. Far less was known about recognition mechanisms in the cellular immune system, for instance in conjunction with the killing of virus-infected cells by T-lymphocytes. One area where cellular immunity had previously been studied in some detail was, however, transplantation biology. It was known that T-lymphocytes could kill cells from a foreign individual after recognition of certain molecules – the major histocompatibility antigens – in the transplant.

The figure describes how a killer T lymphocyte must recognize both the virus antigen and the self histocompatibility antigen molecule in order to kill a virus-infected target cell.

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