Crystal structure of microbial superantigen staphylococcal enterotoxin B at 1.5 Å resolution: implications for superantigen recognition by MHC class II molecules and T-cell receptors

Papageorgiou, Anastassios C.; Tranter, Howard S.; Acharya, K. Ravi

doi:10.1006/jmbi.1997.1577

Cited by 112 publications

(74 citation statements)

References 64 publications

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“…6b). This region has been shown by others to mediate both TCR binding via residues Y90 and Y91 and MHC class II binding via residues Y89, Q92, Y94, and S96 (20,27,37). Jett et al (12) previously found that SEB-induced lymphocyte proliferation could be inhibited by the peptide SEB(61-92) but not SEB(41-70), suggesting that the region for SEB-induced T-cell proliferation involved residues within SEB(70-90).…”

Section: Discussionmentioning

confidence: 92%

“…In contrast, TSST-1, SPEB, and SPEC share little (generally Ͻ25%), if any, sequence similarity with the other toxins (31). However, despite considerable sequence dissimilarity between TSST-1 and the other SEs, their crystal structures reveal striking similarities in conformational architecture (26,27,36,37). For example, TSST-1 and the other PTSAgs all exhibit a two-domain structure with a C-terminal ␤-grasp motif (domain A), a characteristic N-terminal clawlike ␤ barrel (domain B), and a long diagonal ␣ helix separating these two domains (30,31,38).…”

mentioning

confidence: 98%

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Inhibition of Staphylococcal Enterotoxin B-Induced Lymphocyte Proliferation and Tumor Necrosis Factor Alpha Secretion by MAb5, an Anti-Toxic Shock Syndrome Toxin 1 Monoclonal Antibody

2000

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Toxic shock syndrome (TSS) is primarily caused by toxic shock syndrome toxin-1 (TSST-1) and staphylococcal enterotoxin B (SEB). These toxins belong to a family of pyrogenic toxin superantigens (PTSAgs) produced by Staphylococcus aureus and exhibit several shared biological properties, including the induction of massive cytokine release and V␤-specific T-cell proliferation. The crystal structures of most PTSAgs are now published, and they demonstrate a striking similarity in conformational architecture even though their primary protein sequences are different. Despite these structural and immunobiological similarities, no cross-reactivity between TSST-1 and other PTSAgs has been demonstrated in serological or neutralization assays. Our laboratory has developed a neutralizing murine anti-TSST-1 monoclonal antibody (MAb5) which displayed cross-reactivity with SEB by enzyme-linked immunosorbent assay. The aim of the present study was to evaluate whether MAb5 can also cross-neutralize SEB-induced superantigenic activities in vitro. MAb5 was found to partially inhibit SEB-induced T-cell mitogenesis (63%) and tumor necrosis factor alpha (TNF-␣) secretion (70%) in human peripheral blood mononuclear cells (PBMC) in a dose-dependent manner, while an isotypic anti-TSST-1 monoclonal antibody showed no effect. Epitope mapping revealed that MAb5 bound to TSST-1 residues 47 to 56 ( 47 FPSPYYSPAF 56 ) and to SEB residues 83 to 92 ( 83 DVFGANYYYQ 92 ), sequences that located in different regions of these toxins and are structurally dissimilar. SEB peptide 83 DVFG-ANYYYQ 92 was synthesized and found to also inhibit SEB-induced mitogenesis and TNF-␣ secretion in human PBMC. Our results demonstrate for the first time that MAb5 binds to different epitopes on TSST-1 and SEB that appear functionally important in inducing T-cell mitogenesis and TNF-␣ secretion in vitro.

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Section: Discussionmentioning

confidence: 92%

mentioning

confidence: 98%

Inhibition of Staphylococcal Enterotoxin B-Induced Lymphocyte Proliferation and Tumor Necrosis Factor Alpha Secretion by MAb5, an Anti-Toxic Shock Syndrome Toxin 1 Monoclonal Antibody

2000

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“…For example, staphylococcal enterotoxin B and TSS toxin 1 interact with the ␣-chain of MHC class II molecules through N-terminal amino acid residues (3,9). Alternately, the zinc-binding site of SPE C interacts with the ␤-chain of MHC class II molecules through a zinc ion bound to residues in the C-terminal domain as observed in structural studies of SPE C and MHC class HLA-DR2a (DRA*0101,DRB5*0101) ( Fig.…”

mentioning

confidence: 89%

The Zinc-Dependent Major Histocompatibility Complex Class II Binding Site of Streptococcal Pyrogenic Exotoxin C Is Critical for Maximal Superantigen Function and Toxic Activity

et al. 2003

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The cocrystal structure of streptococcal pyrogenic exotoxin C (SPE C) with HLA-DR2a (DRA*0101,DRB5*0101) revealed a zinc-dependent interaction site through residues 167, 201, and 203 on SPE C and residue 81 on the β-chain of HLA-DR2a (DRA*0101,DRB5*0101). Mutation of these SPE C residues resulted in dramatically reduced biological activities. Thus, the zinc-dependent major histocompatibility complex II binding site is critical for maximal biological function of SPE C

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“…Another b-Sag, SED also cross-links MHC class II molecules using Zn 2ϩ (40). In contrast, SEB has a single MHC binding site and does not use Zn 2ϩ (41)(42)(43)(44). Toxic shock syndrome toxin-1 (TSST-1) can bind Zn 2ϩ but does not require it to elicit T cell responses and uses a single site for binding MHC (45,46).…”

Section: Variable Presentation Of B-sag By Mhc Class Ii-positive Cellmentioning

confidence: 99%

Diverse Repertoire of the MHC Class II-Peptide Complexes Is Required for Presentation of Viral Superantigens

Golovkina

Agafonova

Kazansky³

et al. 2001

The Journal of Immunology

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Among other features, peptides affect MHC class II molecules, causing changes in the binding of bacterial superantigens (b-Sag). Whether peptides can alter binding of viral superantigens (v-Sag) to MHC class II was not known. Here we addressed the question of whether mutations limiting the diversity of peptides bound by the MHC class II molecules influenced the presentation of v-Sag and, subsequently, the life cycle of the mouse mammary tumor virus (MMTV). T cells reactive to v-Sag were found in mice lacking DM molecules as well as in AbEp-transgenic mice in which MHC class II binding grooves were predominantly occupied by an invariant chain fragment or Eα52–68 peptide, respectively. APCs from the mutant mice failed to present v-Sag, as determined by the lack of Sag-specific T cell activation, Sag-induced T cell deletion, and by the aborted MMTV infection. In contrast, mice that express I-Ab with a variety of bound peptides presented v-Sag and were susceptible to MMTV infection. Comparison of v-Sag and b-Sag presentation by the same mutant cells suggested that presentation of v-Sag had requirements similar to that for presentation of toxic shock syndrome toxin-1. Thus, MHC class II peptide repertoire is critical for recognition of v-Sag by the T cells and affects the outcome of infection with a retrovirus.

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Crystal structure of microbial superantigen staphylococcal enterotoxin B at 1.5 Å resolution: implications for superantigen recognition by MHC class II molecules and T-cell receptors

Cited by 112 publications

References 64 publications

Inhibition of Staphylococcal Enterotoxin B-Induced Lymphocyte Proliferation and Tumor Necrosis Factor Alpha Secretion by MAb5, an Anti-Toxic Shock Syndrome Toxin 1 Monoclonal Antibody

Inhibition of Staphylococcal Enterotoxin B-Induced Lymphocyte Proliferation and Tumor Necrosis Factor Alpha Secretion by MAb5, an Anti-Toxic Shock Syndrome Toxin 1 Monoclonal Antibody

The Zinc-Dependent Major Histocompatibility Complex Class II Binding Site of Streptococcal Pyrogenic Exotoxin C Is Critical for Maximal Superantigen Function and Toxic Activity

Diverse Repertoire of the MHC Class II-Peptide Complexes Is Required for Presentation of Viral Superantigens

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