Targeting the CD8 co-receptor for therapeutic benefit
CD8 has multiple enhancing effects on early T cell activation events, which include the following: 1) promotion and stabilization of TCR/pMHCI binding at the cell surface; 2) recruitment of essential signaling molecules to the intracellular side of the TCR/CD3/x complex; and 3) localization of TCR/pMHCI complexes within specialized membrane microdomains that act as potentially privileged sites for initiation of the TCR-mediated signaling cascade. CD8 binding also controls the level of T cell cross-reactivity and can differentially affect the deployment of CD8+ T cell effector functions.
CD8 has a potent ability to tune the antigen specific immune response. As such, we are investigating the possibility that targeting CD8 can be used to:
- Block the pathogenic CD8+ T cell attack observed in autoimmune disease and transplant rejection (Mathew Clement).
- Enhance CD8+ T cell immunity especially in a cancer setting where responses are suboptimal (Tamsin Williams).