9630187 Konig The goal of this research project is to elucidate the molecular basis regulating interactions between the T cell coreceptor CD4 and molecules encoded by the major histocompatibility complex class II (MHC Class II). The CD4 glycoprotein interacts with the same MHC class II molecule as the antigen specific T cell receptor, and regulates intrathymic T cell selection and activation of mature T cells. The contribution of the interaction between CD4 and MHC class II molecules to intracellular signal transduction via the antigen specific T cell receptor (TCR) is not known, however the engagement of CD4 by MHC class II molecules contributes quantitatively and qualitatively to the activation of T cells. This project will test the hypothesis that antigen specific T cell receptor mediated signal transduction depends on the structured and sequential oligomerization of TCR, CD4 and MHC class II molecules. The PI has developed assays that measure adhesion of CD4+ T cells to MHC class II cells and to purified MHC class II molecules. Binding data will be correlated with antigen induced T cell responses. Mutations have been introduced into MHC class II molecules to define regions that mediate the interaction with CD4. Mutant MHC class II molecules will be combined with CD4 molecules having mutations in identified MHC class II binding regions to define the interface formed by interacting CD4 and MHC class II molecules. Results from these experiments will enhance our understanding of structure- function relationships responsible for important immune regulatory mechanisms. ***
