Signal Transduction During T Cell Development

Abstract

The CD4 molecule has important roles in signaling during both T cell development and peripheral helper T cell activation^1,2. The ectodomain of CD4 binds to a membrane-proximal domain of MHC class II molecules on antigen presenting cells³, while its cytoplasmic tail interacts with the cytoplasmic protein tyrosine kinase (PTK) p56^lck (lck), a member of the src family of protein tyrosine kinases (reviewed in reference 4). These properties of CD4 contribute to the simultaneous interaction of the T cell antigen receptor (TCR) and CD4 with the same MHC class II molecule and to the localization of lck to the TCR complex. It has been thought that the function of CD4 (and of the class I-specific coreceptor CD8) in signal transduction is to facilitate localization of lck within the TCR complex, thus initiating a PTK signaling cascade. However, recent studies suggest that the primary function of CD4 may be to physically stabilize the interaction of the TCR with MHC, and that a direct signaling role of the CD4-associated lck molecule may not be required^4,5. In this chapter, we discuss a non-catalytic role of the CD4-associated lck molecule in facilitating T cell activation and developmental signaling.