Structural plasticity in antigen selection - Werner - BBSRC

Our bodies have evolved an intricate and powerful system to distinguish self from non-self called the immune system. This formidable task force allows us fight off foreign invaders such as viruses and bacterial pathogens. Since it can cause devastation and disease when it is going wrong, e.g. by attacking the self, such as in auto immune diseases, it needs to be highly regulated and finely tuned. The proposed research investigates a key process to regulate to power of the immune system. Almost every cell in an individual constantly presents samples of short protein fragments from the inside of the cell to the immune system. If these samples are recognised as foreign, the cell will be destroyed. Hence, the control over which peptide samples are shown to the immune system constitutes a key control mechanism to direct the immune response. We are investigating the molecular mechanism of how these representative samples are selected at the cellular level and at the molecular level. We propose that the ability of the protein, called MHC, that recognises the peptides to be malleable and change shape is essential to perform the selection task. We hope that by understanding the molecular nature of this recognition process and its relationship to directing the immune response we will in the future develop new ways of fighting diseases such as cancer and auto-immune diseases by directing an individual's capacity to eradicate what it perceives as non-self.