Projectdetails

The function of a major part of the cells of the immune system is unknown. Most of our knowledge of the immune system concerns conventional T cells, which form only a minority of T cells in tissues. Because of this focus on conventional T cells, the importance of unconventional T cells has been underestimated. In humans, unconventional T cells become activated during infection with Mycobacterium tuberculosis and many other pathogens, but the nature of the antigens, and how they are recognized has been studied in just a few cases. The mouse has been widely used as a model animal to study unconventional T cells. However, there are considerable differences between mice and humans with respect to unconventional T cells. In cattle, several unconventional T cell populations are present that are homologous to their human counterparts and absent in mice. The aim of this proposal is to unravel the function of unconventional T cells and the molecules they recognize, using cattle as a model. The crystal structure and the antigen binding capacities of four molecules that stimulate unconventional T cells, three of which are lacking in mice, will be solved. Their cellular expression pattern and trafficking at subcellular level will be studied to obtain insights in the source of the T cell-stimulating antigens they present. Also, the phenotype and function of T cells that are stimulated by the four selected molecules will be studied. Because cattle is a natural host for mycobacterial infections, unconventional T cells can be studied during these infections. Besides being an excellent model for human mycobacterial diseases, cattle is a species of high priority because of its economic importance and because of its role as a host of several zoonotic diseases, like bovine tuberculosis.