title: Broad T cell immunity to the LcrV virulence protein is induced by targeted delivery to DEC-205/CD205-positive mouse dendritic cells.
abstract: 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.
authors: Laboratory of Cellular Physiology and Immunology and Chris Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York 10065-6399, USA.
authors: Yoonkyung
authors: Y
authors: Do
authors: Chae Gyu
authors: CG
authors: Park
authors: Young-Sun
authors: YS
authors: Kang
authors: Sung Ho
authors: SH
authors: Park
authors: Rebecca M
authors: RM
authors: Lynch
authors: Haekyung
authors: H
authors: Lee
authors: Bradford S
authors: BS
authors: Powell
authors: Ralph M
authors: RM
authors: Steinman
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D017951:Antigen Presentation / Q000276:immunology; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology*; D015153:Blotting, Western; D003713:Dendritic Cells / Q000276:immunology*; D004591:Electrophoresis, Polyacrylamide Gel; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D037181:Lectins, C-Type / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D015778:Minor Histocompatibility Antigens; D010931:Plague Vaccine / Q000276:immunology*; D052899:Pore Forming Cytotoxic Proteins / Q000235:genetics / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D015010:Yersinia pestis / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D015703:Antigens, CD; C093569:DEC-205 receptor; D018984:Epitopes, T-Lymphocyte; C043908:LcrV protein, Yersinia; D037181:Lectins, C-Type; D015778:Minor Histocompatibility Antigens; D010931:Plague Vaccine; D052899:Pore Forming Cytotoxic Proteins; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D007371:Interferon-gamma