Targeting antigen to mouse dendritic cells via Clec9A induces potent CD4 T cell responses biased toward a follicular helper phenotype

J Immunol. 2011 Jul 15;187(2):842-50. doi: 10.4049/jimmunol.1101176. Epub 2011 Jun 15.

Abstract

Three surface molecules of mouse CD8(+) dendritic cells (DCs), also found on the equivalent human DC subpopulation, were compared as targets for Ab-mediated delivery of Ags, a developing strategy for vaccination. For the production of cytotoxic T cells, DEC-205 and Clec9A, but not Clec12A, were effective targets, although only in the presence of adjuvants. For Ab production, however, Clec9A excelled as a target, even in the absence of adjuvant. Potent humoral immunity was a result of the highly specific expression of Clec9A on DCs, which allowed longer residence of targeting Abs in the bloodstream, prolonged DC Ag presentation, and extended CD4 T cell proliferation, all of which drove highly efficient development of follicular helper T cells. Because Clec9A shows a similar expression pattern on human DCs, it has particular promise as a target for vaccines of human application.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Animals
  • Antigen Presentation / genetics
  • Antigen Presentation / immunology*
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • CD4-Positive T-Lymphocytes / classification
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cytotoxicity Tests, Immunologic* / methods
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Humans
  • Immunophenotyping* / methods
  • Lectins, C-Type / genetics
  • Lectins, C-Type / metabolism*
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Minor Histocompatibility Antigens
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • Receptors, Mitogen / genetics
  • Receptors, Mitogen / metabolism
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / chemical synthesis
  • Recombinant Fusion Proteins / metabolism
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism
  • Vaccines, DNA / chemical synthesis
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology

Substances

  • Adjuvants, Immunologic
  • Antigens, CD
  • CLEC12A protein, human
  • CLEC12A protein, mouse
  • CLEC9a protein, human
  • Clec9a protein, mouse
  • DEC-205 receptor
  • Lectins, C-Type
  • Minor Histocompatibility Antigens
  • Receptors, Cell Surface
  • Receptors, Immunologic
  • Receptors, Mitogen
  • Recombinant Fusion Proteins
  • Vaccines, DNA