1996 Nobel Prize in Medicine and Physiology.

Peter C. DohertyRolf M. ZinkernagelThe 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"



 

THE SPECIFICITY OF CELL-MEDIATED IMMUNE RESPONSE

The main goal of the research conducted by Peter Doherty and Rolf Zinkernagel was to study how the immune system, particularly T-cells which are involved in cellular immune response, could protect mice from a virus that causes LCM or Lymphocytic Choriomeningitis. Doherty and Zinkernagel injected LCM-immune T-cells into immunosuppressed, virus-infected recipients. The T-cells home equally well to lymphoid tissue of mice from the same strain and mice from another strain. Surprisingly, they found that the T-cells continue to multiply only in the mice from the same strain. This means that replication is not triggered by the virus, but is dependent on the thymus-derived lymphocytes exposed to histocompatible, virus-infected target cells.






In a similar study, they also found that the T-lymphocytes, despite their reactivity with the virus, were not able to kill the virus-infected cells from a different strain of mice. This means that being infected with the virus is not the only factor considered by the T-cells for them to attack the virus-infected cells. The virus-infected cells must also be histocompatible with the T-cells. This means that T-cells from a strain of mice will not attack virus-infected cells of another strain of mice because they are not histocompatible.



The next logical question is how does the T-lymphocyte recognize histocompatible virus-infected cells? The answers to their question were proteins encoded by the Major Histocompatibility Complex that are expressed on the surface of cells which displays self antigens. This histocompatibility antigen enables the T-cells to recognize self molecules. Integrating all the results that they were able to gather, they concluded that the cellular immune response needs to simultaneously recognize both foreign molecules and self molecules via histocompatibiliy antigens.



Succeeding researches conducted by other scientists showed that if a cell is infected by a virus, a small part of that virus is displayed bound to the cell’s histocompatibility antigen on the cell’s surface. The complex formed by the virus and histocompatibility antigen serves as the signal for the T-cell receptors to recognize the virus-infected cells.



CLINICAL RELEVANCE


The most immediate impact of this discovery was on the field of research. As mentioned above, the discovery of the virus-histocompatibility antigen complex was triggered by this discovery. Our increased knowledge concerning the specificity of cellular immune response enables us to strengthen beneficial immune reactions. On the other hand, that same knowledge also enables us to diminish or change unwanted immune reactions towards the body's own tissue, such as those occurring in rheumatic diseases. This discovery also triggered the development of new vaccines that will protect us against all these infectious diseases.