The extensive diversity of human MHC proteins is the main reason that individuals who receive a foreign organ transplant must be treated with strong immunosuppressive drugs to prevent the immunological rejection of the grafted organ. Of all the foreign proteins that the graft expresses, the MHC proteins are by far the most powerful stimulators of the recipient’s T cells, which would rapidly destroy the graft if they were not prevented from doing so by such drugs. Foreign MHC proteins are powerful T cell stimulants because T cells respond to them in the same way they respond to self MHC proteins that have foreign peptides bound to them; for this reason, the proportion of a person’s T cells that can specifically recognize any foreign MHC protein is relatively high.
cD4 and cD8 co-receptors on T cells Bind to Invariant parts of Mhc proteins
The affinity of TCRs for peptide–MHC complexes on an APC is usually too low by itself to mediate a functional interaction between the two cells. T cells normally require accessory receptors to help stabilize the interaction by increasing the overall strength of the cell–cell adhesion. Unlike TCRs or MHC proteins, the accessory receptors are invariant and do not bind to foreign peptides. Once bound to the surface of a dendritic cell, for example, a T cell increases the strength of the binding by activating an integrin adhesion protein (discussed in Chapter 19), which then binds more strongly to an Ig-like protein on the surface of the dendritic cell. This increased adhesion enables the T cell to remain bound long enough to become activated.
When an accessory receptor has a direct role in activating the T cell by generating its own intracellular signals, it is called a co-receptor. The most important and best understood of the co-receptors on T cells are the CD4 and CD8 proteins, both of which are single-pass transmembrane proteins with extracellular Ig-like domains. Like TCRs, they recognize MHC proteins, but, unlike TCRs, they bind to invariant parts of the MHC protein, far away from the peptide-binding groove. CD4 is expressed on both helper T cells and regulatory T cells and binds to class II MHC proteins, whereas CD8 is expressed on cytotoxic T cells and binds to class I MHC proteins (Figure 24–40).
CD4 and CD8 contribute to T cell recognition by helping the T cell to focus on particular MHC proteins, and thereby on particular types of target cells. Thus, the recognition of class I MHC proteins by CD8 allows cytotoxic T cells to focus on any type of infected host cell, while the recognition of class II MHC proteins by CD4 allows helper and regulatory T cells to focus on the target immune cells that they help or suppress, respectively. The cytoplasmic tail of the CD4 and CD8 proteins is associated with a member of the Src family of cytoplasmic tyrosine kinases
Figure 24–40 CD4 and CD8 co-receptors on the surface of T cells. cytotoxic T cells (Tc) express cD8, which recognizes class I Mhc proteins, whereas helper T cells  (Th) and regulatory T cells (not shown) express cD4, which recognizes class II Mhc proteins. Note that the co-receptors bind to the same Mhc protein that the Tcr has engaged, so that they are brought together with Tcrs during the antigen-recognition process. Whereas the Tcr binds to the variable (polymorphic) parts of the Mhc protein that form the peptide-binding groove, the co-receptor binds to the invariant part, well away from the binding groove.
(discussed in Chapter 15) called Lck, which phosphorylates various intracellular proteins on tyrosines and thereby participates in the activation of the T cell (discussed later).