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Structural basis for the neutralization and specificity of Staphylococcal enterotoxin B against its MHC Class II binding site
- Source :
- mAbs. 6:119-129
- Publication Year :
- 2013
- Publisher :
- Informa UK Limited, 2013.
-
Abstract
- Staphylococcal enterotoxin (SE) B is among the potent toxins produced by Staphylococcus aureus that cause toxic shock syndrome (TSS), which can result in multi-organ failure and death. Currently, neutralizing antibodies have been shown to be effective immunotherapeutic agents against this toxin, but the structural basis of the neutralizing mechanism is still unknown. In this study, we generated a neutralizing monoclonal antibody, 3E2, against SEB, and analyzed the crystal structure of the SEB-3E2 Fab complex. Crystallographic analysis suggested that the neutralizing epitope overlapped with the MHC II molecule binding site on SEB, and thus 3E2 could inhibit SEB function by preventing interaction with the MHC II molecule. Mutagenesis studies were done on SEB, as well as the related Staphylococcus aureus toxins SEA and SEC. These studies revealed that tyrosine (Y)46 and lysine (K)71 residues of SEB are essential to specific antibody–antigen recognition and neutralization. Substitution of Y at SEA glutamine (Q)49, which corresponds to SEB Y46, increased both 3E2’s binding to SEA in vitro and the neutralization of SEA in vivo. These results suggested that SEB Y46 is responsible for distinguishing SEB from SEA. These findings may be helpful for the development of antibody-based therapy for SEB-induced TSS.
- Subjects :
- medicine.drug_class
Immunology
chemical and pharmacologic phenomena
Enterotoxin
Biology
Monoclonal antibody
medicine.disease_cause
Neutralization
Microbiology
Antibodies, Monoclonal, Murine-Derived
Enterotoxins
Mice
Bacterial Proteins
Report
medicine
Animals
Immunology and Allergy
Binding site
Neutralizing antibody
Mice, Inbred BALB C
MHC class II
Binding Sites
Histocompatibility Antigens Class II
Toxic shock syndrome
hemic and immune systems
medicine.disease
Antibodies, Bacterial
Antibodies, Neutralizing
Shock, Septic
biological factors
Staphylococcus aureus
Mutagenesis, Site-Directed
biology.protein
Subjects
Details
- ISSN :
- 19420862 and 19420870
- Volume :
- 6
- Database :
- OpenAIRE
- Journal :
- mAbs
- Accession number :
- edsair.doi.dedup.....0ac7ecde0a30f90c92db6cd659dbd95f