The Structure of the CD4 and CD8 Genes

The CD4 and CD8 glycoproteins are nonpolymorphic members of the immunoglobulin gene superfamily which are expressed on the surface of functionally distinct populations of T lymphocytes. These molecules, also known respectively as T4/Leu3 and T8/Leu2 in human, and as L3T4 and Lyt2/Lyt3 in mouse, appear to be essential for effective cell-cell inter­ actions, resulting either in target cell lysis or in activation of T lymphocytes. Expression of the CD4 and CD8 molecules correlates with the specificity of T cells for either class-II or class-I major histocompatibility complex (MHC) molecules on target cells (1-7). Thus, CD4 and CD8 may serve to increase the avidity of cell-cell interactions by directly binding to mono­ morphic determinants of the appropriate MHC molecule on target cells (2, 8, 9). The view that the CD4 and CD8 molecules act solely as avidity enhan­ cers has been challenged by recent findings which suggest that these mol­ ecules have a role in transmembrane signal transduction (10-14a). However, no experiments to date have directly tested the ability of CD4 or CD8 to bind ligand or to transduce physiologically relevant signals. It is also not known whether CD4 and CD8 perform analogous functions on separate populations of T cells. The basis for intra thymic selection of CD4+ and CD8+ cells that express appropriate MHC-restricted receptors likewise remains a mystery. The elucidation of these problems awaits functional experiments utilizing the newly isolated genes that encode the CD4 and CD8 glycoproteins (15-24). The emphasis of this review hence is on the isolation and structure of these genes and on the glimpses that the predicted structures of the glycoproteins give us into their potential