View the Current Issue

Article

  • The EMBO Journal (2007) 26, 1187 - 1197
  • doi:10.1038/sj.emboj.7601531

Published online: 1 February 2007

Structural basis of T-cell specificity and activation by the bacterial superantigen TSST-1

Beenu Moza1,a, Ashok K Varma1, Rebecca A Buonpane2, Penny Zhu1, Christine A Herfst3, Melissa J Nicholson4, Anne-Kathrin Wilbuer4,5, Nilufer P Seth4, Kai W Wucherpfennig4,5,6, John K McCormick3, David M Kranz2 and Eric J Sundberg1

  1. Boston Biomedical Research Institute, Watertown, MA, USA
  2. Department of Biochemistry, University of Illinois, Urbana, IL, USA
  3. Department of Microbiology and Immunology, Lawson Health Research Institute, University of Western Ontario, London, Ontario, Canada
  4. Department of Cancer Immunology and AIDS, Dana Farber Cancer Research Institute, Harvard Medical School, Boston, MA, USA
  5. Program in Immunology, Harvard Medical School, Boston, MA, USA
  6. Department of Neurology, Harvard Medical School, Boston, MA, USA

Correspondence to:

Eric J Sundberg, Boston Biomedical Research Institute, 64 Grove Street, Watertown, MA 02472, USA. Tel.: +1 617 658 7882; Fax: +1 617 972 1761; E-mail: sundberg@bbri.org

aThese authors contributed equally to this work

Received 7 October 2006; Accepted 7 December 2006

Superantigens (SAGs) bind simultaneously to major histocompatibility complex (MHC) and T-cell receptor (TCR) molecules, resulting in the massive release of inflammatory cytokines that can lead to toxic shock syndrome (TSS) and death. A major causative agent of TSS is toxic shock syndrome toxin-1 (TSST-1), which is unique relative to other bacterial SAGs owing to its structural divergence and its stringent TCR specificity. Here, we report the crystal structure of TSST-1 in complex with an affinity-matured variant of its wild-type TCR ligand, human T-cell receptor beta chain variable domain 2.1. From this structure and a model of the wild-type complex, we show that TSST-1 engages TCR ligands in a markedly different way than do other SAGs. We provide a structural basis for the high TCR specificity of TSST-1 and present a model of the TSST-1-dependent MHC–SAG–TCR T-cell signaling complex that is structurally and energetically unique relative to those formed by other SAGs. Our data also suggest that protein plasticity plays an exceptionally significant role in this affinity maturation process that results in more than a 3000-fold increase in affinity.

  • Keywords:

    • protein–protein interaction,
    • superantigen,
    • surface plasmon resonance,
    • T-cell activity,
    • X-ray crystallography