Surface chimeric receptors as tools in study of lymphocyte activation

In this chapter we have described a powerful technology that has allowed the functional dissection of individual subunits from oligomeric receptors. We have focused primarily on chimeras derived from antigen receptors or their downstream signaling components to illustrate the wide utility of the approach; however, the technology has been applied to numerous multimeric receptors of the immune system including cytokine receptors, Fc receptors, and natural killer (NK) cell inhibitory receptors. Although the significance of the structural complexity of oligomeric receptors is by no means understood, it is certain that valuable benefits must be derived from the integrated function of their subunits. In the case of antigen receptors, the multiplicity of ITAMs likely allows the cell to distinguish subtle variations in ligand affinities with exquisite sensitivity. Clearly, an isolated subunit that is ligated with antibodies cannot confer such complex function. For instance, it cannot reveal the subtle changes in signal transduction that likely occur on stimulation with altered antigenic peptide ligands or during a complex cell-cell interaction. However, before the intricacies of integrated receptor function can be appreciated, the potential or unique functional properties contributed by each individual receptor component must first be understood. Providing a tool to acquire this kind of understanding has been the greatest asset of this technology. Acknowledging its limitations, the use of surface chimeric receptors remains an invaluable approach toward our understanding the complex function of oligomeric receptors.