ROLE OF CD4 AND CD8 IN T-CELL ACTIVATION AND DIFFERENTIATION

This chapter summarizes the role of CD4 and CD8 in both T cell activation and differentiation. CD4 and CD8 are cell surface glycoproteins expressed on T lymphocytes that have specificity for class II or class I major histocompatibility complex (MHC) proteins, respectively. These proteins play major roles in both the activation of mature peripheral T cells and the thymic differentiation process that leads to the mature T cell repertoire and the expression of CD4 and CD8 on mutually exclusive T cell subsets. The crystal structures of immunoglobulin-like domains of CD4 and CD8 are determined, binding sites for CD8 on class I MHC proteins and CD4 on class II MHC proteins are mapped, and both proteins are shown to be associated via their cytoplasmic tails with the relatively T cell specific, src-family tyrosine kinase p56lck. The first indication that CD4 and CD8 may play a more active role in T cell receptor (TCR)-mediated cell signaling came from studies demonstrating that anti-CD4 and anti-CD8 monoclonal antibodies inhibited mitogen-induced activation in the absence of relevant MHC ligands. © 1993, Academic Press Inc.