28 Feb 2014
Rolf Zinkernagel and Peter Doherty

In 1973 Rolf Zinkernagel came from Switzerland to the John Curtin School of Medical Research in Canberra, Australia, where he met Peter Doherty. Together they studied basic aspects of the immune defence against virus infections in different strains of mice. Their discoveries illustrate how findings within basic biological research can give rise to conclusions with wide implications for society and fundamentally new therapeutic approaches in clinical medicine.

Doherty and Zinkernagel found that white blood cells - or more precisely killer T cells - from one mouse strain - recognise and kill virus-infected cells from another mouse strain only if the two mouse strains carry the same variant of transplantation antigens. From this apparently simple observation they, and subsequently a whole generation of immunologists, were able to find new approaches and new solutions to a series of fundamental immunological problems.

As a result of this discovery, it became possible to understand that the true function of transplantation antigens is not to provide an obstacle to transplantation. Instead, their function is to bind and present molecules from viruses and other microorganisms to white blood cells in such a way that the white blood cells understand whether they should become aggressive or stay calm. As a consequence it became obvious how each individual, thanks to his/her unique set of transplantation antigens, also carries his/her unique immune system. It also became possible to understand why evolution has created these large immunological differences between us as individuals within a species. Immunological diversity is advantageous for the single individual as well as for the species. Thus, there will always be some individuals that survive even severe epidemics. In return, individuals carrying a certain variant of transplantation antigens have an increased susceptibility to autoimmune diseases such as rheumatoid arthritis or multiple sclerosis, and this is possibly the price that these individuals pay for the fact that their forefathers survived a severe epidemic.

These discoveries have deeply influenced the understanding of fundamental issues in basic and clinical immunology. Subsequent research has made it easier not only to understand, but also to change the immune system. Our increased knowledge enables us to strengthen beneficial immune reactions, for example in cases of otherwise insufficient responses towards invading microorganisms or against cancer metastasis. This knowledge should also enable us to diminish or change unwanted immune reactions towards the body's own tissue, such as those occurring in rheumatic diseases.   (Edited version of the Nobel Presentation speech, Stockholm 1997)

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