CD8 is a two chain glycoprotein which is expressed on the surface of circulating T-cells.
T-cell antigen recognition, and subsequent T-cell activation, is dominated by the interaction between the TCR and pMHC. However, T-cell activation is often enhanced through the close cooperation of the TCR with a co-receptor. There are two T-cell co-receptors; CD8, and CD4. CD8 was first discovered as a cell surface marker in mice and was used to distinguish between CD8+ CTLs and CD4+ Th cells. CD8 exists as both a heterodimer (CD8αβ) and a homodimer (CD8αα) of which the former is expressed on the majority of CTLs. CD8 has been shown to be involved in CTL co-activation by increasing antigen sensitivity, and by stabilising the TCR/pMHC interaction. In order to carry out these roles, the CD8 co-receptor binds to a distinct invariant region of the pMHCI molecule, compared to the TCR, allowing the potential for tripartite (TCR/pMHC/CD8) complex formation. The main interface between CD8αα and pMHCI is between CD8 residues 51-55 and pMHC residues 223-229 in the α3-domain, which form a CD8 binding loop.
Although CD8 is most often described as a T-cell co-receptor because it has important role in T-cell signalling, via p56lck, to induce TCR mediated T-cell activation signals, work in our lab and others has shown that the CD8 co-receptor is also important for; CD8+ T-cell development, stabilisation of the interface between CD8+ T-cells and target cells, and activation of intestinal epithelial T lymphocytes (iIELs). Therefore, CD8 has been the target of many therapeutic strategies designed to modulate T-cell responses during auto-immune reactions, allergy and organ transplant rejection.