scholarly journals Structure of the staphylococcal enterotoxin B vaccine candidate S19 showing eliminated superantigen activity

2017 ◽  
Vol 73 (11) ◽  
pp. 595-600
Author(s):  
Woo Hyeon Jeong ◽  
Dong Hyun Song ◽  
Gyeung Haeng Hur ◽  
Seong Tae Jeong
Keyword(s):  
Structural Change ◽  
Mhc Class Ii ◽  
Vaccine Candidate ◽  
Complex Structure ◽  
Cell Receptor ◽  
Staphylococcal Enterotoxin ◽  
Staphylococcal Enterotoxin B ◽  
Loop Region ◽  
T Cell Receptor Beta ◽  
Enterotoxin B

Four mutations (N23A, Y90A, R110A and F177A) were introduced into S19, a vaccine candidate for staphylococcal enterotoxin B (SEB), resulting in a lower binding affinity towards the T-cell receptor beta chain (TCB) and reducing its superantigen activity. The structure of S19 was solved and was superposed on the native or complex structure of SEB. In the superposition model, mutations that were introduced seemed to reduce the number of hydrogen bonds at the SEB–TCB interface. S19 also displayed an unexpected structural change around the flexible-loop region owing to the Y90A mutation. This local structural change provided evidence that the mutated form of S19 could have a lower affinity for major histocompatibility complex (MHC) class II than wild-type SEB.

scholarly journals Mutations defining functional regions of the superantigen staphylococcal enterotoxin B.

1992 ◽  
Vol 175 (2) ◽  
pp. 387-396 ◽  
Author(s):  
J W Kappler ◽  
A Herman ◽  
J Clements ◽  
P Marrack
Keyword(s):  
T Cell ◽  
Mhc Class Ii ◽  
Cell Receptor ◽  
Class Ii ◽  
Staphylococcal Enterotoxin ◽  
Staphylococcal Enterotoxin B ◽  
Rapid Weight Loss ◽  
Functional Regions ◽  
T Cell Stimulation ◽  
Enterotoxin B

Staphylococcal enterotoxin B (SEB) is both a superantigen and toxin. As a superantigen, SEB can bind to major histocompatibility complex (MHC) class II molecules to form a ligand for alpha/beta T cell receptors bearing particular V beta elements. As a toxin, SEB causes rapid weight loss in mice sometimes leading to death. We show here that both of these functions map to the NH2-terminal portion of the toxin. Three regions were identified: one important in MHC class II binding, one in T cell recognition, and one in both functions. These results support the conclusion that the toxicity of SEB is related to massive T cell stimulation and release of cytokine mediators and show that the residues interacting with MHC and the T cell receptor are intertwined.

scholarly journals Contribution of the flexible loop region to the function of staphylococcal enterotoxin B

2010 ◽  
Vol 23 (5) ◽  
pp. 415-421 ◽  
Author(s):  
Saeko Yanaka ◽  
Motonori Kudou ◽  
Yoshikazu Tanaka ◽  
Takumi Sasaki ◽  
Sumiyo Takemoto ◽  
...  
Keyword(s):  
Staphylococcal Enterotoxin ◽  
Staphylococcal Enterotoxin B ◽  
Flexible Loop ◽  
Loop Region ◽  
Enterotoxin B

scholarly journals Potent Neutralization of Staphylococcal Enterotoxin B In Vivo by Antibodies that Block Binding to the T-Cell Receptor

2019 ◽  
Vol 431 (21) ◽  
pp. 4354-4367 ◽  
Author(s):  
Gang Chen ◽  
Hatice Karauzum ◽  
Hua Long ◽  
Danielle Carranza ◽  
Frederick W. Holtsberg ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Staphylococcal Enterotoxin ◽  
Staphylococcal Enterotoxin B ◽  
Enterotoxin B ◽  
Potent Neutralization

scholarly journals Structural basis for the neutralization and specificity of Staphylococcal enterotoxin B against its MHC Class II binding site

mAbs ◽  
2013 ◽  
Vol 6 (1) ◽  
pp. 119-129 ◽  
Author(s):  
Tian Xia ◽  
Shuaiyi Liang ◽  
Huajing Wang ◽  
Shi Hu ◽  
Yuna Sun ◽  
...  
Keyword(s):  
Binding Site ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Staphylococcal Enterotoxin ◽  
Structural Basis ◽  
Staphylococcal Enterotoxin B ◽  
Enterotoxin B

scholarly journals The toxicity of staphylococcal enterotoxin B in mice is mediated by T cells.

1990 ◽  
Vol 171 (2) ◽  
pp. 455-464 ◽  
Author(s):  
P Marrack ◽  
M Blackman ◽  
E Kushnir ◽  
J Kappler
Keyword(s):  
Weight Loss ◽  
T Cells ◽  
T Cell ◽  
Mhc Class Ii ◽  
Cell Function ◽  
Class Ii ◽  
Staphylococcal Enterotoxin ◽  
Staphylococcal Enterotoxin B ◽  
Rapid Weight Loss ◽  
Enterotoxin B

Staphylococcal enterotoxin B (SEB) has been shown in the past to be a potent T cell stimulant in mouse or man. The toxin acts as a superantigen that is, it binds to class II MHC proteins and, as such a complex, stimulates T cells bearing particular V beta s as part of their receptors. The toxin also has several pathological effects, causing, in mice, rapid weight loss, thymus atrophy, immunosuppression, and, at high doses, death. The data in this paper show that at least one of these effects, weight loss, is T cell mediated. Staphylococcal enterotoxin-mediated weight loss is MHC dependent, and is almost absent in animals expressing MHC class II molecules, which, complexed with SEB, are poor T cell stimulants. Also, mice that lack T cell function, genetically or because of cyclosporin A treatment, lose no or less weight than controls in response to SEB. Finally, animals bred such that they express few T cells bearing V beta s with which SEB can interact lose much less weight in response to the toxin than littermate controls that have higher numbers of reactive T cells. It is therefore suggested that the pathological effects of the staphylococcal, T cell-stimulating toxins in mouse and man may be partially or wholly the consequence of massive T cell stimulation.

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