Toll-like Receptor Recognition Regulates Immunodominance in an Antimicrobial CD4+ T Cell Response

Felix Yarovinsky, Holger Kanzler, Sara Hieny, Robert L. Coffman, Alan Sher

Research output: Contribution to journalArticle

111 Scopus citations

Abstract

Although Toll-like Receptors (TLRs) play a major function in innate recognition of pathogens, their role in antigen processing and presentation in vivo is poorly understood. Here we establish that Toxoplasma gondii profilin, a TLR11 ligand present in the parasite, is an immunodominant antigen in the CD4+ T cell response to the pathogen. The immunogenicity of profilin was entirely dependent on both TLR11 recognition and signaling through the adaptor myeloid differentiation factor 88 (MyD88). Selective responsiveness to this parasite protein was regulated at the level of antigen presentation by dendritic cells (DC) and required both TLR signaling and major histocompatibility complex (MHC) class II recognition acting in cis. These findings support a major influence of TLR recognition in antigen presentation by DC in vivo and establish a mechanism by which TLR ligand association regulates the immunogenicity of microbial antigens.

Original languageEnglish (US)
Pages (from-to)655-664
Number of pages10
JournalImmunity
Volume25
Issue number4
DOIs
StatePublished - Oct 1 2006

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Keywords

  • CELLIMMUNO
  • MOLIMMUNO
  • PROTEINS

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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