4 - Role of CD4 and CD8 in Determining Cell Fate in the Thymus

Abstract

CD8 and CD4 are cell surface receptors that are expressed on non-overlapping sets of mature T cells. CD8 binds to class I major histocompatibility complex (MHC) molecules and is found on T cells that have an antigen receptor (TCR) that is restricted to class I MHC molecules. CD4 binds to class II MHC molecules and is found on class II-specific T cells. CD8 and CD4 expression correlates with T cell effector function: CD4+ class II-specific T cells are predominantly helper T cells, whereas CD8+ class I-specific T cells have cytotoxic activity. CD8 and CD4 are required for efficient recognition of peptide-MHC complexes by mature T cells. Although several T cell surface molecules are required for efficient T cell responses, CD8 and CD4 are unique because they function in concert with the TCR, by binding to the same MHC molecules. This property has led to the designation of CD8 and CD4 as coreceptors. In addition to their role in mature T cell responses to foreign peptide and MHC molecules, CD4 and CD8 are involved in the recognition of self MHC molecules, which occurs during thymic development. To survive and mature, thymocytes must recognize self MHC molecules as they develop in a process known as “positive selection.”