CD28: Direct and Critical Receptor for Superantigen Toxins

Every adaptive immune response requires costimulation through the B7/CD28 axis, with CD28 on T-cells functioning as principal costimulatory receptor. Staphylococcal and streptococcal superantigen toxins hyperstimulate the T-cell-mediated immune response by orders of magnitude, inducing a lethal cytokine storm. We show that to elicit an inflammatory cytokine storm and lethality, superantigens must bind directly to CD28. Blocking access of the superantigen to its CD28 receptor with peptides mimicking the contact domains in either toxin or CD28 suffices to protect mice effectively from lethal shock. Our finding that CD28 is a direct receptor of superantigen toxins broadens the scope of microbial pathogen recognition mechanisms.

• Publication year

  2013

• Venue

  Toxins

• Publication date

  2013-09-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3390/toxins5091531PMID 24022021PMCID 3798871
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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  2001influential reference
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  2001cited by this paper
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  2000influential reference
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  1999cited by this paper
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  1998cited by this paper
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  1996cited by this paper
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  1996influential reference
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  1996cited by this paper
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  1996cited by this paper
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  1995cited by this paper
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  1994cited by this paper
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  1994cited by this paper
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  1994cited by this paper
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  1993cited by this paper
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  1993cited by this paper
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  1992cited by this paper
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  1990cited by this paper

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