W0129

Three-dimensional Structure of the Complex between a T-cell Receptor ß-chain and the Superantigen SEB Hongmin Li¹, Andrea Llera¹, Lukas Leder¹, Daisuke Tsuchiya¹, Xavier Ysern², Patrick M. Schliever³, Klaus Karjalainen⁴, Roy A. Mariuzza¹, ¹Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, 9600 Gudelsky Drive, Rockville, MD 20850 USA, ²Center for Drug Evaluation and Research, FDA, 5600 Fishers Lane, Rockville, MD 20857 USA, ³University of Minnesota Medical School, Minneapolis, MN 55455 USA, ⁴Basel Institute for Immunology, Grenzacherstrasse 487, Postfach CH-4005, Basel, Switzerland

The three-dimensional structures of a T-cell antigen receptor ß-chain (mouse Vß8.2-Jß2.1-Cß1), bound to a bacterial superantigen (SAG), Staphylococcus aureus enterotoxin B (SEB), and to the mutant SEB Val26_Tyr, have been determined at high resolution (2.4Å and 2.6Å, respectively) by means of X-ray crystallography. Mutant and wild type SEB bind to the ß chain of the TCR in a way similar to Staphylococcus aureus enterotoxins C2 and C3 (SEC2/SEC3) (Fields et al., 1996). In each case, the ß chain binds in a cleft between the two domains of the SAG. The complementary-determining region 2 (CDR2) of the ß chain contributes the principal contacts to the SAGs, with part of hypervariable region 4 (HV4) and framework regions 2 and 3 (FR2 and FR3) also involved in TCR-SAG recognition. As in the ß-SEC3 structure, there are no contacts between Vß CDR3 and SEB. However, in contrast to the ß-SEC3 structure, there are also no contacts between Vß CDR1 and SEB due to a dramatically different disulfide loop conformation in the SEB and SEC3 structures. The main interaction between Vß8.2 and SEB involves several conserved hydrogen bonds between SEB side chain atoms and Vß8.2 main chain atoms, as well as numerous van de Waals contacts. A small number of conformational changes in both SEB and the ß-chain occur upon complex formation, indicating an "induced fit" mechanism for TCR-SAG recognition. Based on the high resolution structures, a TCR-SAG-MHC tri-complex was built, and a series of comparisons with TCRs and SAGs of known structures were performed. These comparisons provide rational insights into the molecular basis for TCR recognition by Staphylococcus aureus enterotoxins.

Fields, B.A. et al. (1996), Nature, 384, 188-192.