The CD family of co-receptors are a well-studied group of extracellular receptors found in immunological cells. The CD receptor family typically act as co-receptors, illustrated by the classic example of CD4 acting as a co-receptor to the T cell receptor (TCR) to bind major histocompatibility complex II (MHC-II). This binding is particularly well-studied in T-cells where it serves to activate T-cells that are in their resting (or dormant) phase and to cause active cycling T-cells to undergo programmed cell death. Boehme et al. demonstrated this interesting dual outcome by blocking the binding of CD4 to MHC-II which prevented the programmed cell death reaction that active T-cells typically display.
The CD4 receptor is composed of four concatamerized Ig-like domains and is anchored to the cell membrane by a single transmembrane domain. CD family receptors are typically monomers or dimers, though they are all primarily extracellular proteins. The CD4 receptor in particular interacts with murine MHC-II following the "ball-on-stick" model, where the Phe-43 ball fits into the conserved hydrophobic α2 and β2 domain residues. During binding with MHC-II, CD4 maintains independent structure and does not form any bonds with the TCR receptor.
The members of the CD family of co-receptors have a wide range of function. As well as being involved in forming a complex with MHC-II with TCR to control T-cell fate, the CD4 receptor is infamously the primary receptor that HIV envelope glycoprotein GP120 binds to. In comparison, CD28 acts as a ‘co-coreceptor’ (costimulatory receptor) for the MHC-II binding with TCR and CD4. CD28 increases the IL-2 secretion from the T-cells if it is involved in the initial activation; however, CD28 blockage has no effect on programmed cell death after the T-cell has been activated.