Structure of the Superantigen Staphylococcal Enterotoxin B in Complex with TCR and Peptide–MHC Demonstrates Absence of TCR–Peptide Contacts

Abstract

Superantigens are immune-stimulatory toxins produced by Staphylococcus aureus, which are able to interact with host immune receptors to induce a massive release of cytokines, causing toxic shock syndrome and possibly death. In this article, we present the x-ray structure of staphylococcal enterotoxin B (SEB) in complex with its receptors, the TCR and MHC class II, forming a ternary complex. The structure, in combination with functional analyses, clearly shows how SEB adopts a wedge-like position when binding to the β-chain of TCR, allowing for an interaction between the α-chain of TCR and MHC. Furthermore, the binding mode also circumvents contact between TCR and the peptide presented by MHC, which enables SEB to initiate a peptide-independent activation of T cells.

Biological toxins of potential bioterrorism risk: Current status of detection and identification technology

“…C) 3D structure of STX and its producer, the dinoflagellate Alexandrium ostenfeldii (insert). D) Crystal structure of SEB in complex with MHC II and T cell receptor (4C56.pdb [93]) (SEB red ribbon, intrachain disulfide bridge yellow sticks, MHC II yellow ribbon, TCR green ribbon) and EM picture of Staphylococcus aureus producing SE (insert). substrates; the detection limits are mostly in the low ng/mL to high pg/mL-range [21,22].…”

Bacterial superantigens and superantigen-like toxins

“…The recently solved ternary structure of SEB in complex with HLA-DR1 and TcRVα22/Vβ19 confirmed that SEB adopts a wedgelike position when binding to the TcRVβ-chain, allowing for an interaction between the Vα chain and MHC class II (Figure 32.3a). This binding mode also circumvents contact between TcR and the presented peptide, allowing SEB to trigger a peptide-independent activation of T cells [190]. In 2002, two more complexes were determined-that of SPE-A bound to mouse Vβ8.2 and of SPE-C bound to human TcRVβ2.1 [18].…”

Allergy—A New Role for T Cell Superantigens of Staphylococcus aureus?

“…However, due to their extremely high mitogenic activity, only fragments or toxoids, i.e., SAg mutants lacking the ability to cross-link TCR and MHC-II, can be used for vaccination. The structure-function relationship of several SAgs has been resolved in the past 25 years [6,[38][39][40][41][42][43][44]. On that basis, inactivating mutations have been predicted and experimentally confirmed for a number of staphylococcal SAgs [45][46][47].…”