The CD8 and co-receptor

CD8 is a two chain glycoprotein which is expressed on the surface of circulating killer T-cells. This molecule is used to define killer T-cells and they are often called “CD8 T-cells” (this distinguishes then from CD4 T helper T-cells).

What is the role of CD8 in the immune system?
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.

When the TCR engages foreign pMHC, CD8 plays an important role in signal transduction by recruiting a critical kinase, called Lck, to the intracellular side of the TCR/CD3 complex. CD8 also serves to stabilise the TCR/pMHC interaction and locate the TCR to specialised membrane regions that are enriched for molecules needed for TCR-mediated signal transduction.