T Cell Reactive Tetramers for Virus Infections in Pigs

Virus infections in livestock are constant threats to animal welfare and productivity all over the world. In this project we will deliver new advanced technological reagents for measurement of the cytotoxic cells of the immune system with activity against virus infected cells in pigs. This will be an extremely important tool in the development of new efficacious vaccines against diseases like foot- and mouth disease and influenza.
All cells op the body exhibit small fragments of their contents on the cell surface. A virus infected cell will therefore display fragments of virus proteins which, like a key in a lock on the cytotoxic cell, will activate killing of the infected cell. This will stop replication of the virus and this cell-mediated immunity is therefore a crucial part of the host defence against virus infections.
The virus-key is made up of host tissue-type molecules displaying a small virus peptide (a chain of 8 to 11 amino acids). We will produce luminescent recombinant virus-keys, MHC class I tetramers, for pigs, which will enable us to directly stain and identify host cell with cytotoxic activity against virus. With these tetramers we can determine exactly which peptides in the virus proteins that mediate the desired immune response, and thereby which virus components that can be used in new targeted vaccines. Furthermore, we will be able to measure if vaccines have induced the desired cytotoxic effector cells, and we can develop computer models to predict peptide antigens of new viruses.
The project group consists of scientists from Technical University of Denmark, Copenhagen University and leading American scientists in virus infections and MHC molecules in pigs.