Broad T cell immunity to the LcrV virulence protein is induced by targeted delivery to DEC-205/CD205-positive mouse dendritic cells

Eur J Immunol. 2008 Jan;38(1):20-9. doi: 10.1002/eji.200737799.


There is a need for a more efficient vaccine against the bacterium Yersinia pestis, the agent of pneumonic plague. The F1-LcrV (F1-V) subunit vaccine in alhydrogel is known to induce humoral immunity. In this study, we utilized DC to investigate cellular immunity. We genetically engineered the LcrV virulence protein into the anti-DEC-205/CD205 mAb and thereby targeted the conjugated protein directly to mouse DEC-205(+) DC in situ. We observed antigen-specific CD4(+) T cell immunity measured by intracellular staining for IFN-gamma in three different mouse strains (C57BL/6, BALB/c, and C3H/HeJ), while we could not observe such T cell responses with F1-V vaccine in alhydrogel. Using a peptide library for LcrV protein, we identified two or more distinct CD4(+) T cell mimetopes in each MHC haplotype, consistent with the induction of broad immunity. When compared to nontargeted standard protein vaccine, DC targeting greatly increased the efficiency for inducing IFN-gamma-producing T cells. The targeted LcrV protein induced antibody responses to a similar extent as the F1-V subunit vaccine, but Th1-dependent IgG2a and IgG2c isotypes were observed only after anti-DEC-205:LcrV mAb immunization. This study sets the stage for the analysis of functional roles of IFN-gamma-producing T cells in Y. pestis infection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibody Formation / immunology
  • Antigen Presentation / immunology
  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / immunology*
  • Antigens, CD / immunology*
  • Blotting, Western
  • Dendritic Cells / immunology*
  • Electrophoresis, Polyacrylamide Gel
  • Epitopes, T-Lymphocyte / immunology
  • Interferon-gamma / metabolism
  • Lectins, C-Type / immunology*
  • Lymphocyte Activation / immunology
  • Mice
  • Minor Histocompatibility Antigens
  • Plague Vaccine / immunology*
  • Pore Forming Cytotoxic Proteins / genetics
  • Pore Forming Cytotoxic Proteins / immunology*
  • Receptors, Cell Surface / immunology*
  • Recombinant Fusion Proteins / immunology
  • Th1 Cells / immunology*
  • Yersinia pestis / immunology


  • Antibodies, Monoclonal
  • Antigens, Bacterial
  • Antigens, CD
  • DEC-205 receptor
  • Epitopes, T-Lymphocyte
  • LcrV protein, Yersinia
  • Lectins, C-Type
  • Minor Histocompatibility Antigens
  • Plague Vaccine
  • Pore Forming Cytotoxic Proteins
  • Receptors, Cell Surface
  • Recombinant Fusion Proteins
  • Interferon-gamma