Albany 2001

category image Biomolecular
SUNY at Albany
June 19-23, 2001

Structural Basis of T Cell Activation by Bacterial Superantigens

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 Vb domain of the T cell receptor (TCR) and with major histocompatibility complex (MHC) class II molecules on the surface of antigen-presenting cells. We have determined the crystal structure of streptococcal pyrogenic exotoxin C (SPE-C) in complex with a human class II protein, HLA-DR2a, bearing a self-peptide from myelin basic protein (MBP). SPE-C binds the b chain through a zinc bridge that links the SAG and class II molecules. Surprisingly, SPE-C also makes extensive contacts with the MBP peptide, such that peptide accounts for one-third of the surface area of the MHC molecule buried in the complex, similar to TCR-peptide/MHC complexes. Thus, SPE-C may optimize T cell responses by mimicking the peptide dependence of conventional antigen presentation and recognition. We have also determined the structure of SPE-C bound to a human TCR b domain. These, and other, structures demonstrate that bacterial SAGs have evolved diverse strategies for engaging TCR and MHC molecules, yet with the same end result: highly efficient T cell activation, comparable to that by specific peptide/MHC complexes.

Yi Li(1), Eric Sundberg(1), Hongmin Li(2), Patrick M. Schlievert(3), Klaus Karjalainen(4), and Roy A. Mariuzza(1)

Center for Advanced Research in Biotechnology(1), University of Maryland Biotechnology Institute, 9600 Gudelsky Drive, Rockville, MD 20850 Wadsworth Center(2), New York State Department of Health, Empire State Plaza, PO Box 509, Albany, NY 12201-0509 Department of Microbiology(3), University of Minnesota School of Medicine, Minneapolis, MN 55455 Basel Institute for Immunology(4), Grenzacherstrasse 487, Postfach CH-4005, Basel, Switzerland