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LCMV (1974)


Lymphocytic choriomeningitis virus (LCMV) is a common infection of rodents and was first identified as long ago as the 1930s. It causes inflammation in the meninges, the lining of the brain and spinal cord and frequently infects the house mouse. The virus has, however, played a crucial role in the history of immunology, specifically the discovery of the role played by the major histocompatibility complex (MHC) in controlling the deadly potential of T-lymphocytes to kill virus-infected cells.

But first a bit of background. The immune system consists of two kinds of white blood cells, the B- and T- lymphocytes. The B-lymphocytes are involved in antibody-mediated immunity while the T-lymphocytes are behind cell-mediated immunity. In the 1970s far less was known about cell-mediated immunity, except that it was important in transplantation biology because T-cell could kill cells from a foreign individual after recognition of certain molecules – the major histocompatibility complex – in the transplant.

Then along came Peter Doherty and Rolf Zinkernagel, working at the John Curtin School of Medical Research in Canberra, Australia. They found that mice infected with the LCMV virus developed killer T-cells which could destroy virus-infected cells in a test tube. However, this was only true when the cells in the test tube came from the same genetic strain of mice. When they used another mouse strain, the T-cells were not able to kill the LCMV-infected cells.

In pioneering studies published in 1974, they showed that the killer potential of the T-cells relied on the “correct” variant of the MHC, in other words the same MHC molecules as the infected mouse that had produced the T-cells. Zinkernagel's and Doherty's findings demonstrated conclusively the requirement for the cellular immune system to recognise simultaneously both “foreign” molecules from the LCMV virus and the “self-molecules”, or major histocompatibility antigens.

The discovery described what became known as MHC restriction and had important ramifications for transplant medicine. What also became obvious was the important function of the major histocompatibility antigens, called HLA-antigens in humans, in and individual´s normal immune response.

Not surprisingly perhaps, the two scientists shared the 1996 Nobel prize in physiology or medicine.