Crystal structure of a superantigen bound to the high-affinity, zinc-dependent site on MHC class II

Immunity. 2001 Jan;14(1):93-104. doi: 10.1016/s1074-7613(01)00092-9.


MHC class II molecules possess two binding sites for bacterial superantigens (SAGs): a low-affinity site on the alpha chain and a high-affinity, zinc-dependent site on the beta chain. Only the former has been defined crystallographically. We report the structure of streptococcal pyrogenic exotoxin C (SPE-C) complexed with HLA-DR2a (DRA*0101, DRB5*0101) bearing a self-peptide from myelin basic protein (MBP). SPE-C binds the beta chain through a zinc bridge that links the SAG and class II molecules. Surprisingly, SPE-C also makes extensive contacts with the MBP peptide, such that peptide accounts for one third of the surface area of the MHC molecule buried in the complex, similar to TCR-peptide/MHC complexes. Thus, SPE-C may optimize T cell responses by mimicking the peptide dependence of conventional antigen presentation and recognition.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / immunology
  • Binding Sites
  • Crystallography, X-Ray
  • Exotoxins / chemistry*
  • Exotoxins / immunology
  • HLA-DR2 Antigen / chemistry*
  • HLA-DR2 Antigen / immunology
  • Histocompatibility Antigens Class II / chemistry
  • Histocompatibility Antigens Class II / immunology
  • Humans
  • Membrane Proteins*
  • Mice
  • Models, Molecular
  • Myelin Basic Protein / chemistry
  • Protein Structure, Secondary
  • Superantigens / chemistry*
  • Superantigens / immunology
  • Zinc / immunology*


  • Bacterial Proteins
  • Exotoxins
  • HLA-DR2 Antigen
  • Histocompatibility Antigens Class II
  • I-E-antigen
  • Membrane Proteins
  • Myelin Basic Protein
  • SpeA protein, Streptococcus pyogenes
  • Superantigens
  • erythrogenic toxin
  • Zinc

Associated data

  • PDB/1AN8
  • PDB/1FV1
  • PDB/1HQR