EXPRESSION OF T-CELL ANTIGEN RECEPTOR HETERODIMERS IN A LIPID-LINKED FORM

The interaction of the T cell receptor for antigen (TCR) with its antigen-major histocompatibility complex ligand is difficult to study because both are cell surface multimers. The TCR consists of two chains (α and β) that are complexed to the five or more nonpolymorphic CD3 polypeptides. A soluble form of the TCR was engineered by replacing the carboxyl termini of α and β with signal sequences from lipid-linked proteins, making them susceptible to enzymatic cleavage. In this manner, TCR heterodimers can be expressed independently of the CD3 polypeptides and in significant quantities (0.5 milligram per week). This technique seems generalizable to biochemical and structural studies of many other cell surface molecules as well.