Structural basis for differential binding of staphylococcal enterotoxin A and toxic shock syndrome toxin 1 to class II major histocompatibility molecules.

AUTOR(ES)

Pontzer, C H

RESUMO

The related staphylococcal toxins staphylococcal enterotoxin A (SEA) and toxic shock syndrome toxin 1 (TSST-1) are microbial superantigens. They require interaction with class II major histocompatibility complex (MHC) molecules to activate T cells. We have previously identified a binding site on SEA, the N-terminal 45 amino acids, as well as its corresponding receptor on the MHC antigen, residues 65-85 of the beta chain. To further characterize the structural basis for SEA binding to class II MHC molecules we have examined its relationship to TSST-1 binding. Both toxins bound similarly to murine A20 cells, but blockage of binding was observed only with the homologous toxin, which suggests that the binding sites for the two toxins on A20 cells are distinct. In contrast, specific binding of SEA was greater than that of TSST-1 on human Raji cells. Further, SEA was a better inhibitor of TSST-1 binding than was TSST-1 itself at low concentrations, but TSST-1 only minimally inhibited SEA binding. The data suggest that TSST-1 interacts with Raji cells at an SEA binding site, but with a lower affinity. The peptides SEA-(1-45) and I-A beta b-(65-85) were capable of blocking SEA binding on both A20 and Raji cells, but blockage was more effective on A20 cells. Neither peptide was capable of blocking TSST-1 binding on either cell line. The data are compatible with a model in which SEA has a binding site on A20 cells involving SEA-(1-45) and I-A beta b-(65-85) which is distinct from that which binds TSST-1, while at least two binding sites are present on Raji cells. One site involves predominantly the residue 1-45 region on SEA and the 65-85 region of the MHC beta chain, while the other site involves both a different region on the SEA molecule and a different site on the class II MHC molecule to which it binds. This latter site also binds TSST-1.

Documentos Relacionados

• Toxic shock syndrome toxin 1 binds to major histocompatibility complex class II molecules.
• Staphylococcal enterotoxin A and toxic shock syndrome toxin compete with CD4 for human major histocompatibility complex class II binding.
• Toxic shock syndrome toxin 1 binds to major histocompatibility complex class II molecules
• Phospholipids enhance the binding of peptides to class II major histocompatibility molecules.
• Effects of pH and polysaccharides on peptide binding to class II major histocompatibility complex molecules.