Forward genetic dissection of afferent immunity: The role of TIR adapter proteins in innate and adaptive immune responses

Bruce Beutler, Kasper Hoebe, Louis Shamel

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

The innate immune system senses pathogens largely through signals initiated by proteins known as 'Toll-like receptors' (TLRs), of which ten representatives are known to be encoded in the human genome. The understanding of the biochemical circuitry that maintains the innate capacity for immune recognition and response has loomed as a major hurdle in immunology. A total of five adapter proteins with cytoplasmic domain homology to the TLRs are known to exist in mammals. These proteins show preferential association with individual TLR family members, giving a particular character to the signals that distinct microorganisms initiate, and also initiate the adaptive immune response. The adaptive immune response is dependent upon upregulation of costimulatory molecules (UCM) such as CD80 and CD86. Forward genetic analysis has revealed that this upregulation depends upon an adapter encoded by a locus known as Lps2, and upon type I interferon receptor signaling.

Original languageEnglish (US)
Pages (from-to)571-580
Number of pages10
JournalComptes Rendus - Biologies
Volume327
Issue number6
DOIs
StatePublished - Jun 1 2004

Keywords

  • 'Toll-like receptors'
  • Adapter proteins
  • Costimulatory molecule expression
  • Human genome
  • Innate immune system
  • TLR family
  • Type I interferon

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)

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