CD4, CD8 AND THE ROLE OF CD45 IN T-CELL ACTIVATION

CD4, CD8 and CD45 regulate the coupling of the T-cell receptor complex (CD3-TCR) to tyrosine kinase activation and phosphorylation of key su bstrates such as phospholipase Cgamma1. CD4 and CD8 contribute to acti vation signals through their cytoplasmic association with p56lck. Expr ession of the zeta-chain is required for functional synergy of the T-c ell receptor with CD4 in the activation of phospholipase Cgamma1, whic h probably reflects an interaction between p56lck and zeta-associated kinase ZAP-70. CD45 expression is required for CD3-TCR signaling. CD45 may positively regulate signaling by dephosphorylating the carboxyl-t erminal tyrosine of p56lck and p59fyn, and negatively regulate signali ng by dephosphorylation of other TCR-associated substrates directly. O ne ligand for CD45 receptor has been identified as the B cell CD22 mol ecule. The positive and negative effects of CD45 are sensitive to the composition of CD45 in receptor complexes, and may be regulated by spe cific associations of CD45 isoforms with other receptors such as CD3-T CR, CD2 and CD4.