Crystal Structure of Staphylococcal Enterotoxin I (SEI) in Complex with a Human MHC Class II Molecule.

FERNÁNDEZ MM; GUAN R; SWAMINATTAN C; MALCHIODI EL; MARIUZZA RA

JOURNAL OF BIOLOGICAL CHEMISTRY

Año: 2006 vol. 281 p. 25356 - 25364

0021-9258

Superantigens are bacterial or viral proteins that elicit massiveT cell activation through simultaneous binding to majorhistocompatibility complex (MHC) class II and T cell receptors.This activation results in uncontrolled release of inflammatorycytokines, causing toxic shock. A remarkable property of superantigens,which distinguishes them from T cell receptors, istheir ability to interact with multiple MHC class II alleles independentlyof MHC-bound peptide. Previous crystallographicstudies have shown that staphylococcal and streptococcal superantigensbelonging to the zinc family bind to a high affinity siteon the class II
-chain. However, the basis for promiscuousMHC recognition by zinc-dependent superantigens is not obvious,because the
-chain is polymorphic and the MHC-boundpeptide forms part of the binding interface. To understand howzinc-dependent superantigens recognize MHC, we determinedthe crystal structure, at 2.0 A˚ resolution, of staphylococcal enterotoxinI bound to the human class II molecule HLA-DR1 bearinga peptide from influenza hemagglutinin. Interactions betweenthe superantigen and DR1
-chain are mediated by a zincion, and 22% of the buried surface of peptide
MHC is contributedby the peptide. Comparison of the staphylococcal enterotoxinI
peptide
DR1 structure with ones determined previouslyrevealed that zinc-dependent superantigens achieve promiscuousbinding toMHCby targeting conservatively substituted residuesof the polymorphic
-chain. Additionally, these superantigenscircumvent peptide specificity by engaging MHC-boundpeptides at their conformationally conserved N-terminal regionswhile minimizing sequence-specific interactions withpeptide residues to enhance cross-reactivity.