W0226: Crystal Structures of Streptococcal Superantigens Complexed with T Cell Receptor Beta Chains

Crystal Stuctures of Streptococcal Superantigens Complexed with T Cell Receptor β Chains. Hongmin Li^1*, Eric Sundberg^2*, Patrick M. Schlievert³, Klaus Karjalainen⁴, Roy A. Mariuzza². ¹Wadsworth Center, New York State Dept. of Health, Empire State Plaza, PO Box 509, Albany, NY 12201, ²Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, 9600 Gudelsky Dr., Rockville, MD 20850, ³Dept. of Microbiology, University of Minnesota School of Medicine, Minneapolis, MN 55455, ⁴Basel Institute for Immunology, Grenzacherstrasse 487, Postfach CH-4005, Basel, Switzerland.

Staphylococcal enterotoxins and streptococcal pyrogenic exotoxins are typical bacterial superantigens (SAGs) that can simultaneously bind to major histocompatibility complex (MHC) class II molecules and to T-cell receptor (TCR), resulting in the stimulation of a large number of T-cells expressing specific V( elements of the TCR repertoire. Here we report the crystal structures of streptococcal pyrogenic exotoxin A (SPE-A) complexed with a 14.3.d TCR β chain and of streptococcal pyrogenic exotoxin C (SPE-C) complexed with a Vβ2-bearing β chain. The SPE-A-β-chain complex is formed in a mode very similar to those of staphylococcal SAG-TCR (-chain complexes (Fields et al., 1996; Li et al., 1998), in which the CDR2 and FR3 of TCR Vβ make majority interactions with SPE-A and there is no direct contact between SPE-A and Vβ CDR3. In addition, the CDR1 residues of TCR Vβ8.2 form hydrogen bonds with the disulfide loop residues of superantigen SPE-A, which was not seen in other complexes. In contrast, the binding mode of SPE-C-β-chain complex is considerably different from the above-mentioned SAG-TCR complexes. The SPE-C simultaneously interacts with all CDR loops of the Vβ2-bearing TCR β chain. Thus, although the SAGs perform similar biological functions, their binding modes to MHC (Li et al., 2001) and to TCR vary considerably.