Transcriptional programming of dendritic cells for enhanced MHC class II antigen presentation

Nat Immunol. 2014 Feb;15(2):161-7. doi: 10.1038/ni.2795. Epub 2013 Dec 22.


CD11b(+) dendritic cells (DCs) seem to be specialized for presenting antigens via major histocompatibility (MHC) class II complexes to stimulate helper T cells, but the genetic and regulatory basis for this is not established. Conditional deletion of Irf4 resulted in loss of CD11b(+) DCs, impaired formation of peptide-MHC class II complexes and defective priming of helper T cells but not of cytotoxic T lymphocyte (CTL) responses. Gene expression and chromatin immunoprecipitation followed by deep sequencing (ChIP-Seq) analyses delineated an IRF4-dependent regulatory module that programs enhanced MHC class II antigen presentation. Expression of the transcription factor IRF4 but not of IRF8 restored the ability of IRF4-deficient DCs to efficiently process and present antigen to MHC class II-restricted T cells and promote helper T cell responses. We propose that the evolutionary divergence of IRF4 and IRF8 facilitated the specialization of DC subsets for distinct modes of antigen presentation and priming of helper T cell versus CTL responses.

MeSH terms

  • Animals
  • Antigen Presentation / genetics*
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Dendritic Cells / immunology*
  • Gene Expression Profiling
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / immunology
  • Histocompatibility Antigens Class II / genetics
  • Histocompatibility Antigens Class II / immunology*
  • Interferon Regulatory Factors / genetics
  • Interferon Regulatory Factors / metabolism*
  • Lymphocyte Activation / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Protein Binding / genetics
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Transgenes / genetics


  • Histocompatibility Antigens Class II
  • Interferon Regulatory Factors
  • interferon regulatory factor-4
  • interferon regulatory factor-8

Associated data

  • GEO/GSE52773