A structural and functional comparison of staphylococcal enterotoxins A and C2 reveals remarkable similarity and dissimilarity

Schad, Elinor; Papageorgiou, Anastassios C.; Svensson, L.A.; Acharya, K. Ravi

doi:10.1006/jmbi.1997.1023

Cited by 39 publications

(20 citation statements)

References 44 publications

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“…Thus, we assume that residues 11-18, particularly aa 13-18, are significant for SEC2 activity. Crystallographic studies have shown that aa 13-18 of SEC2 comprise a helix (a2) that could stabilize the conformation of the region participating in both MHC II and T-cell receptor binding (Schad et al, 1997;Papageorgiou et al, 2004). In this study, we deleted aa 1-13 of SEC2 and found that the deletion did not affect the T-cell proliferation activity, thereby confirming our assumption.…”

Section: Discussionsupporting

confidence: 83%

“…*P,0.05 compared with the SEC2 group at same time point. three b-sheets (b6, b7 and b8; Schad et al, 1997), among which only b8 is a possible binding site for the MHC molecule. Thus, we assumed that aa 129-163 were also not required for the T-cell proliferation activity of SEC2.…”

Section: Discussionmentioning

confidence: 99%

“…The molecular architecture of the SE family has been studied extensively to explore the relationship between their structure and function (Schad et al, 1997;Papageorgiou et al, 2004). In most cases, an SE molecule consists of two closely spaced N-and C-terminal domains.…”

Section: Introductionmentioning

confidence: 99%

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T-cell proliferation and antitumour activities of a truncated mutant of staphylococcal enterotoxin C2 with decreased cytokine secretion

Zhou

Liu

et al. 2013

Journal of Medical Microbiology

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As a superantigen, staphylococcal enterotoxin C2 (SEC2) has commonly been used as an antitumour immunotherapy agent in China. However, the clinical application of SEC2 has been hampered by its pyrogenic toxicity and the presence of neutralizing antibody in patients. Thus, an improvement in its superantigen-based immunotherapy is highly needed. In this study, a truncated SEC2 mutant, SEC(14-128), was constructed without the N-terminal 13 and C-terminal 111 aa. This mutant retained T-cell proliferation and antitumour activities in in vitro experiments. However, it induced a significantly decreased release of the main inflammatory cytokines inerleukin-2 and gamma interferon. Moreover, SEC(14-128) exhibited reduced toxicity and affinity to anti-SEC2 IgG compared with native SEC2. Based on the considerable antitumour activity and low toxicity, it is proposed that the mutant SEC(14-128) could be a potential candidate for cancer treatment.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

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T-cell proliferation and antitumour activities of a truncated mutant of staphylococcal enterotoxin C2 with decreased cytokine secretion

Zhou

Liu

et al. 2013

Journal of Medical Microbiology

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“…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: 99%

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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“…The interaction of toxic shock syndrome toxin with MHCII differed from that of SEB in that it spanned the antigen-binding cleft and was influenced by the peptides present in the antigenbinding cleft [2,3]. The discovery that Zn 2ϩ ions participated in the superantigen binding process [4,5], coupled with the availability of high-resolution crystal structures [6][7][8] indicate that multiple epitopes on MHCII would be important to regulatory function of these molecules. Indeed, mutagenesis of amino acid residues 47, 187, or 225 of SEA attenuated the stimulatory activity of the molecule, apparently by disrupting cross-linking [5], and provided an explanation for our 1991 observations that SEA was a more potent agonist than SEB [9].…”

Section: Introductionmentioning

confidence: 99%

Complex high affinity interactions occur between MHCI and superantigens

Chapes

Herpich

1998

Journal of Leukocyte Biology

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Staphylococcal enterotoxins A and C1 (SEA or SEC1) bound to major histocompatibility-I (MHCI) molecules with high affinity (binding constants ranging from 1.1 M to 79 nM). SEA and SEC1 directly bound MHCI molecules that had been captured by monoclonal antibodies specific for H-2K k , H-2D k , or both. In addition, MHCIspecific antibodies inhibited the binding of SEC1 to LM929 cells and SEA competitively inhibited SEC1 binding; indicating that the superantigens bound to MHCI on the cell surface. The affinity and number of superantigen binding sites differed depending on whether MHCI was expressed in the membrane of LM929 cells or whether it was captured. These data support the hypothesis that MHCI molecules can serve as superantigen receptors. J. Leukoc. Biol. 64: 587-594; 1998.

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A structural and functional comparison of staphylococcal enterotoxins A and C2 reveals remarkable similarity and dissimilarity

Cited by 39 publications

References 44 publications

T-cell proliferation and antitumour activities of a truncated mutant of staphylococcal enterotoxin C2 with decreased cytokine secretion

T-cell proliferation and antitumour activities of a truncated mutant of staphylococcal enterotoxin C2 with decreased cytokine secretion

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

Complex high affinity interactions occur between MHCI and superantigens

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