Abstract
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.
Highlights
Staphylococcal enterotoxin B (SEB) is one of seven toxins secreted by Staphylococcus aureus, and is classified as a bacterial superantigen (Balaban & Rasooly, 2000)
We focused on interactions between the T-cell receptor beta chain (TCB) and SEB, which directly activate the immune system without involving major histocompatibility complex (MHC) (Rodstrom et al, 2014)
We compared the structures of S19 and SEB in the MHC– SEB–TCB complex (PDB entry 4c56)
Summary
Staphylococcal enterotoxin B (SEB) is one of seven toxins secreted by Staphylococcus aureus, and is classified as a bacterial superantigen (Balaban & Rasooly, 2000). SEB is one of the group II superantigens (Sundberg et al, 2007), a group that includes SEC and SpeA Superantigens in this group bind to T-cell receptors (TCRs) in a peptide-independent manner to generate an abrupt and strong immune response (Hewitt et al, 1992; Fraser, 2011). This 28 kDa toxin consists of two domains, domain I (amino acids 30–120) and domain II (amino acids 127–239), which are composed of a -barrel structure and antiparallel -sheets, respectively. The candidate induces fewer cytokines upon in vivo administration, and in this study we provide the structure of S19 to explain the exact effect of the introduced mutations on its in vivo characteristics
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