Three-Dimensional Structure of the Complex between a T Cell Receptor β Chain and the Superantigen Staphylococcal Enterotoxin B

Abstract

Superantigens (SAGs) are a class of immunostimulatory proteins of bacterial or viral origin that activate T cells by binding to the V beta domain of the T cell antigen receptor (TCR). The three-dimensional structure of the complex between a TCR beta chain (mouse V beta8.2) and the SAG staphylococcal enterotoxin B (SEB) at 2.4 A resolution reveals why SEB recognizes only certain V beta families, as well as why only certain SAGs bind mouse V beta8.2. Models of the TCR-SEB-peptide/MHC class II complex indicate that V alpha interacts with the MHC beta chain in the TCR-SAG-MHC complex. The extent of the interaction is variable and is largely determined by the geometry of V alpha/V beta domain association. This variability can account for the preferential expression of certain V alpha regions among T cells reactive with SEB.

The Staphylococcal Enterotoxins

“…The SE-TCR interaction appears to play a pivotal role in the superantigenic activity of SEs. Indeed, a direct correlation has been established between SE affinity for the TCR and its ability to stimulate T cells (Li et al, 1998b).…”

The structure of superantigen complexed with TCR and MHC reveals novel insights into superantigenic T cell activation

“…There is currently no available structural information regarding how group III SAgs engage TCRs, which may be a consequence of the expected low affinity between the class III SAgs and the TCRs. Previous structural studies of SAgs from other classes engaging the variable β-domain of TCR (SEB, SEC 2 − 3 , SEK, TSST-1, SPE-A and SPE-C) use only the single β-chain of TCR [7][8][9][10][11] , and often, there are mutations in the TCR or SAg. To date, there is one report on structural studies of an SAg from mycoplasma (Mycoplasma arthritidis mitogen, MAM) in complex with TCR and MHC, showing specific contacts between the SAg and both variable α-domain of TCR (TCRVα) and variable β-domain of TCR (TCRVβ).…”

Identification of MHC Class II-Associated Peptides That Promote the Presentation of Toxic Shock Syndrome Toxin-1 to T Cells

“…amino terminus of the peptide might affect SEA presentation (5, 7) and TSST-1 (5, 6, 9), whereas no clear peptide effects have been shown for SEB presentation (4,8,36,37). One of the problems in analyzing the presentation of SAgs with the T2-I-A b tumor line system is that there is no clear positive control (the parental DMpositive T1-I-A b parental line expresses human class II molecules), unless a peptide is defined that clearly promotes superantigen presentation.…”

“…B acterial superantigens (SAg) 4 are toxins that hyperstimulate the immune system through the direct activation of T cells and APCs (1). SAg exposure often induces a severe, sometimes lethal, toxic shock-like syndrome, which is accompanied by fever and immune dysfunction (2).…”

“…SAg exposure often induces a severe, sometimes lethal, toxic shock-like syndrome, which is accompanied by fever and immune dysfunction (2). The activity of SAgs is mediated through the cross-linking of MHC class II molecules on the APC with the TCR on the T cell (3,4). Recent studies from our laboratory and others have shown that MHC class II-associated peptides have a profound impact on this interaction (5)(6)(7)(8).…”