Question

How do CD4 and CD8 coreceptors facilitate signaling through the TCR?

Answer 1

The CD8 and CD4 cells increase signaling of T cells by attaching to the MHC I (CD8) or MHC II (CD4) molecules on the APCs. The contact of the CD4 molecule with MHC II significantly decreases the number of antigenic peptides necessary for T cell activation and significantly increases cytokine formation by the help of the helper T cells. Similarly, the CD8 and MHC I interaction increases the sensitivity of antigen and the reaction of Tc (cytotoxic T cells) cells to the pMHC ligands.

The major role of the CD8 and CD4 co-receptors is to employ the Src tyrosine kinase enzyme (Lck) to the TCR and pMHC complex subsequent co-receptor binding to the MHC molecule, resultant in the gathering of a TCR, MHC, CD8 or TCR, MHC, CD4 ternary complex. The binding of Lck occurs through its involvement through the cytoplasmic tail of CD8 or CD4 molecule.

The additional increase in the small concentration of Lck encourages phosphorylation of the ITAMs (immunoreceptor tyrosine activation motifs) in the CD₃ cytoplasmic tails subunits linked with the TCR in the TCR and CD3 complex, resulting into the employment and activation of molecule known as Zap-70. The activated Zap-70 phosphorylates the SLP-76 and the LAT, which function as scaffolds to employ additional signaling molecules to the downstream position of T cell signaling machinery that regulates T cell activation, propagation, and differentiation.