ArticlePLoS biology2011
Binding of superantigen toxins into the CD28 homodimer interface is essential for induction of cytokine genes that mediate lethal shock.
Article in PLoS biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 93 papers, 1 of them a synthesis that pooled it.
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Who cites it
93 citing papers in PubMed, 1 synthesis or guideline pooled it, 138 citations in OpenAlex.
- Antimicrobial resistance crisis: could artificial intelligence be the solution?Military Medical Research · 2024Pooled it
- Group A Streptococcal Virulence Factors and Vaccine Development-An Update.Microorganisms · 2026Review
- Microbiome dysbiosis and therapeutic restoration in atopic dermatitis.Frontiers in cellular and infection microbiology · 2026Review
- NKG2A-mediated immune modulation of natural killer cells by Staphylococcus aureus.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Two homologous sequences of Grp78 and HSP70 represent tumor antigens shared with streptococcal superantigens in eliciting an antitumor immune response: an immunoinformatic investigation.Frontiers in immunology · 2025Article
- Subduing the Inflammatory Cytokine Storm.International journal of molecular sciences · 2024Review
- Generation of Novel Tumour-Selective SEA Superantigen-Based Peptides with Improved Safety and Efficacy for Precision Cancer Immunotherapy.International journal of molecular sciences · 2024Article
- Novel insights into the immune response to bacterial T cell superantigens.Nature reviews. Immunology · 2024Review
- Review
- RNA Activators of Stress Kinase PKR within Human Genes That Control Splicing or Translation Create Novel Targets for Hereditary Diseases.International journal of molecular sciences · 2024Article
- Targeting staphylococcal enterotoxin B binding to CD28 as a new strategy for dampening superantigen-mediated intestinal epithelial barrier dysfunctions.Frontiers in immunology · 2024Article
- The homodimer interfaces of costimulatory receptors B7 and CD28 control their engagement and pro-inflammatory signaling.Journal of biomedical science · 2023Article
- Novel SPEA Superantigen Peptide Agonists and Peptide Agonist-TGFαL3 Conjugate. In Vitro Study of Their Growth-Inhibitory Effects for Targeted Cancer Immunotherapy.International journal of molecular sciences · 2023Article
- The superantigens SpeC and TSST-1 specifically activate TRBV12-3/12-4Communications biology · 2023Article
- Bivalent binding of staphylococcal superantigens to the TCR and CD28 triggers inflammatory signals independently of antigen presenting cells.Frontiers in immunology · 2023Article
- Species comparison: human and minipig PBMC reactivity under the influence of immunomodulating compoundsFrontiers in immunology · 2023Article
- Superantigens, a Paradox of the Immune Response.Toxins · 2022Review
- Article
- Analysis of host-pathogen gene association networks reveals patient-specific response to streptococcal and polymicrobial necrotising soft tissue infections.BMC medicine · 2022Article
- CD28 costimulation promotes an antitumor CD8Cellular & molecular immunology · 2022Article
33 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bacterial superantigens, a diverse family of toxins, induce an inflammatory cytokine storm that can lead to lethal shock. CD28 is a homodimer expressed on T cells that functions as the principal costimulatory ligand in the immune response through an interaction with its B7 coligands, yet we show here that to elicit inflammatory cytokine gene expression and toxicity, superantigens must bind directly into the dimer interface of CD28. Preventing access of the superantigen to CD28 suffices to block its lethality. Mice were protected from lethal superantigen challenge by short peptide mimetics of the CD28 dimer interface and by peptides selected to compete with the superantigen for its binding site in CD28. Superantigens use a conserved β-strand/hinge/α-helix domain of hitherto unknown function to engage CD28. Mutation of this superantigen domain abolished inflammatory cytokine gene induction and lethality. Structural analysis showed that when a superantigen binds to the T cell receptor on the T cell and major histocompatibility class II molecule on the antigen-presenting cell, CD28 can be accommodated readily as third superantigen receptor in the quaternary complex, with the CD28 dimer interface oriented towards the β-strand/hinge/α-helix domain in the superantigen. Our findings identify the CD28 homodimer interface as a critical receptor target for superantigens. The novel role of CD28 as receptor for a class of microbial pathogens, the superantigen toxins, broadens the scope of pathogen recognition mechanisms.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.