PmpG 303-311 , a Protective Vaccine Epitope That Elicits Persistent Cellular Immune Responses in Chlamydia muridarum-Immune Mice
Open Access
- 1 June 2012
- journal article
- research article
- Published by American Society for Microbiology in Infection and Immunity
- Vol. 80 (6), 2204-2211
- https://doi.org/10.1128/iai.06339-11
Abstract
Urogenital Chlamydia serovars replicating in reproductive epithelium pose a unique challenge to host immunity and vaccine development. Previous studies have shown that CD4 T cells are necessary and sufficient to clear primary Chlamydia muridarum genital tract infections in the mouse model, making a protective CD4 T cell response a logical endpoint for vaccine development. Our previous proteomics studies identified 13 candidate Chlamydia proteins for subunit vaccines. Of those, PmpG-1 is the most promising vaccine candidate. To further that work, we derived a PmpG 303-311 -specific multifunctional Th1 T cell clone, designated PmpG1.1, from an immune C57BL/6 mouse and used it to investigate the presentation of the PmpG 303-311 epitope by infected epithelial cells. Epithelial presentation of the PmpG 303-311 epitope required bacterial replication, occurred 15 to 18 h postinfection, and was unaffected by gamma interferon (IFN-γ) pretreatment. Unlike epitopes recognized by other Chlamydia -specific CD4 T cell clones, the PmpG 303-311 epitope persisted on splenic antigen-presenting cells (APC) of mice that cleared primary genital tract infections. PmpG1.1 was activated by unmanipulated irradiated splenocytes from immune mice without addition of exogenous Chlamydia antigen, and remarkably, activation of PmpG1.1 by unmanipulated immune splenocytes was stronger 6 months postinfection than it was 3 weeks postinfection. Enhanced presentation of PmpG 303-311 epitope on splenic APC 6 months postinfection reflects some type of “consolidation” of a protective immune response. Understanding the antigen-presenting cell populations responsible for presenting PmpG 303-311 early (3 weeks) and late (6 months) postinfection will likely provide important insights into stable protective immunity against Chlamydia infections of the genital tract.Keywords
This publication has 25 references indexed in Scilit:
- Immunization with Live and DeadChlamydia muridarumInduces Different Levels of Protective Immunity in a Murine Genital Tract Model: Correlation with MHC Class II Peptide Presentation and Multifunctional Th1 CellsThe Journal of Immunology, 2011
- Chlamydia-Specific CD4 T Cell Clones Control Chlamydia muridarum Replication in Epithelial Cells by Nitric Oxide-Dependent and -Independent MechanismsThe Journal of Immunology, 2010
- Chlamydia muridarumT-Cell Antigens Formulated with the Adjuvant DDA/TDB Induce Immunity against Infection That Correlates with a High Frequency of Gamma Interferon (IFN-γ)/Tumor Necrosis Factor Alpha and IFN-γ/Interleukin-17 Double-Positive CD4+T CellsInfection and Immunity, 2010
- Chlamydia muridarum-Specific CD4 T-Cell Clones Recognize Infected Reproductive Tract Epithelial Cells in an Interferon-Dependent FashionInfection and Immunity, 2009
- Characterization of Murine Dendritic Cell Line JAWS II and Primary Bone Marrow-Derived Dendritic Cells inChlamydia muridarumAntigen Presentation and Induction of Protective ImmunityInfection and Immunity, 2008
- Lack of an Effect of Antibiotic Treatment on Prolonged Detection of Chlamydial DNA in Murine Genital Tract InfectionAntimicrobial Agents and Chemotherapy, 2007
- The Unexpected Impact of aChlamydia trachomatisInfection Control Program on Susceptibility to ReinfectionThe Journal of Infectious Diseases, 2005
- Murine Oviduct Epithelial Cell Cytokine Responses toChlamydia muridarumInfection Include Interleukin-12-p70 SecretionInfection and Immunity, 2004
- Chlamydia trachomatisPersistence in the Female Mouse Genital Tract: Inducible Nitric Oxide Synthase and Infection OutcomeInfection and Immunity, 2001
- Monoclonal antibodies directed against T cell epitopes presented by class I MHC antigensInternational Immunology, 1993