Th-1 polarization is regulated by dendritic-cell comparison of MHC class I and class II antigens

Blood. 2009 Apr 30;113(18):4213-23. doi: 10.1182/blood-2008-10-185470. Epub 2009 Jan 26.


In the control of T-helper type I (Th-1) polarization, dendritic cells (DCs) must interpret a complex array of stimuli, many of which are poorly understood. Here we demonstrate that Th-1 polarization is heavily influenced by DC-autonomous phenomena triggered by the loading of DCs with antigenically matched major histocompatibility complex (MHC) class I and class II determinants, that is, class I and II peptide epitopes exhibiting significant amino acid sequence overlap (such as would be physiologically present during infectious processes requiring Th-1 immunity for clearance). Data were derived from 13 independent antigenic models including whole-cell systems, single-protein systems, and 3 different pairs of overlapping class I and II binding epitopes. Once loaded with matched class I and II antigens, these "Th-1 DCs" exhibited differential cytokine secretion and surface marker expression, a distinct transcriptional signature, and acquired the ability to enhance generation of CD8(+) T lymphocytes. Mechanistically, tRNA-synthetases were implicated as components of a putative sensor complex involved in the comparison of class I and II epitopes. These data provide rigorous conceptual explanations for the process of Th-1 polarization and the antigenic specificity of cognate T-cell help, enhance the understanding of Th-1 responses, and should contribute to the formulation of more effective vaccination strategies.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acyl-tRNA Synthetases / metabolism
  • Antigen Presentation
  • Antigens, CD / metabolism
  • Biomarkers / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cells, Cultured
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Flow Cytometry
  • Gene Expression Profiling
  • Histocompatibility Antigens Class I / physiology*
  • Histocompatibility Antigens Class II / physiology*
  • Humans
  • Immunoglobulins / metabolism
  • Interferon-gamma / metabolism
  • Interleukin-12 / metabolism
  • Lymphocyte Activation
  • Membrane Glycoproteins / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Th1 Cells / cytology
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism


  • Antigens, CD
  • Biomarkers
  • CD83 antigen
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Immunoglobulins
  • Membrane Glycoproteins
  • Interleukin-12
  • Interferon-gamma
  • Amino Acyl-tRNA Synthetases