Structures of two streptococcal superantigens bound to TCR β chains reveal diversity in the architecture of T cell signaling complexes

Eric J. Sundberg, Hongmin Li, Andrea S. Llera, John K. McCormick, José Tormo, Patrick M. Schlievert, Klaus Karjalainen, Roy A. Mariuzza

Research output: Contribution to journalArticlepeer-review

94 Scopus citations

Abstract

Superantigens (SAGs) crosslink MHC class II and TCR molecules, resulting in an overstimulation of T cells associated with human disease. SAGs interact with several different surfaces on MHC molecules, necessitating the formation of multiple distinct MHC-SAG-TCR ternary signaling complexes. Variability in SAG-TCR binding modes could also contribute to the structural heterogeneity of SAG-dependent signaling complexes. We report crystal structures of the streptococcal SAGs SpeA and SpeC in complex with their corresponding TCR β chain ligands that reveal distinct TCR binding modes. The SpeC-TCR β chain complex structure, coupled with the recently determined SpeC-HLA-DR2a complex structure, provides a model for a novel T cell signaling complex that precludes direct TCR-MHC interactions. Thus, highly efficient T cell activation may be achieved through structurally diverse strategies of TCR ligation.

Original languageEnglish (US)
Pages (from-to)687-699
Number of pages13
JournalStructure
Volume10
Issue number5
DOIs
StatePublished - 2002
Externally publishedYes

Keywords

  • Major histocompatibility complex
  • Protein-protein interactions
  • Superantigen
  • T cell activation
  • T cell receptor
  • X-ray crystallography

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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