THE STRUCTURAL BASIS OF T CELL ACTIVATION BY SUPERANTIGENS

Abstract

▪ Abstract Superantigens (SAGs) are a class of immunostimulatory and disease-causing proteins of bacterial or viral origin with the ability to activate large fractions (5–20%) of the T cell population. Activation requires simultaneous interaction of the SAG with the Vβ domain of the T cell receptor (TCR) and with major histocompatibility complex (MHC) class II molecules on the surface of an antigen-presenting cell. Recent advances in knowledge of the three-dimensional structure of bacterial SAGs, and of their complexes with MHC class II molecules and the TCR β chain, provide a framework for understanding the molecular basis of T cell activation by these potent mitogens. These structures along with those of TCR-peptide/MHC complexes reveal how SAGs circumvent the normal mechanism for T cell activation by peptide/MHC and how they stimulate T cells expressing TCR β chains from a number of different families, resulting in polyclonal T cell activation. The crystal structures also provide insights into the basi...