Why study CD8+ T-cells?
CD8+ T cells are essential for effective immune defence against intracellular microbes and neoplasia. However CD8+ T cell dysregulation can have devastating effects such as autoimmune disease, leukaemia and transplant rejection.
Unique Recognition System
CD8+ T cells recognize antigenic determinants in the form of short peptides derived from endogenous peptides bound to MHC class I (pMHCI). CD8+ T cell recognition of pMHCI involves the binding of two receptors (T cell receptor; TCR and CD8) to a single ligand (pMHCI), a modus operandi that is unique to ab T cell biology. Therefore CD8+ T cell activation involves two key interactions:
- The TCR/pMHCI interaction: determines antigen specificity. Promiscuity is a characteristic feature of this interaction and it is essential for effective immunity.
- The pMHCI/CD8 interaction: has a potent ability to tune the antigen specific immune response by a number of different mechanisms.
Figure 1: Interaction between TCR MHCI and CD8
We are interesting in understanding both of these interactions and how to manipulate them for therapeutic benefit.