STRUCTURE OF A SUPERANTIGEN T-CELL RECEPTOR CHAIN COMPLEX. Roy A. Mariuzza¹, Hongmin Li¹, Emilio L. Malchiodi¹, Xavier Ysern², Cynthia V. Stauffacher³, Patrick M. Schlievert⁴, Klaus Karjalainan⁵, Barry A. Fields^{1, 1}Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, 9600 Gudelsky Drive, Rockville, MD 20850, U.S.A., ²Center for Drug Evaluation and Research, F.D.A., 5600 Fishers Lane, Rockville, MD 20857, U.S.A., ³Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, U.S.A., ⁴Department of Microbiology, University of Minnesota Medical School, Minneapolis, MN 55455, U.S.A., ⁵Basel Institute for Immunology, Grenzacherstrasse 487, Postfach CH-4005, Basel, Switzerland

Superantigens (SAgs) are potent stimulators of the immune system that have been implicated in several major human diseases including rheumatoid arthritis, diabetes mellitus and tuberculosis. SAgs interact with the antigen receptor on T cells as well as molecules of the major histocompatibility complex (MHC) on the surface of antigen presenting cells. These interactions result in the stimulation of an unusually large fraction of the T-cell population. The crystal structure of a SAg that causes food-poisoning, Staphylococcus aureus enterotoxin C3 (SEC3), bound to the chain of a T- cell antigen receptor (TCR) has been determined at 3 Å resolution using the high resolution crystal structures of the uncomplexed components as molecular replacement search models. Complementarity determining regions 1 and 2, and, to a lesser extent, hypervariable region 4 of the TCR chain bind in a cleft between the two domains of the SAg. The crystal structure of this complex, along with that of an MHC-SAg complex has enabled the construction of a model for the ternary TCR-SAg-MHC complex. The functional implications of these structures will be discussed.