title: PmpG303-311, a protective vaccine epitope that elicits persistent cellular immune responses in Chlamydia muridarum-immune mice.
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.
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA. raymjohn@iupui.edu
authors.forename: Raymond M
authors.initials: RM
authors.lastname: Johnson
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.forename: Micah S
authors.initials: MS
authors.lastname: Kerr
authors.forename: James E
authors.initials: JE
authors.lastname: Slaven
authors.forename: Karuna P
authors.initials: KP
authors.lastname: Karunakaran
authors.forename: Robert C
authors.initials: RC
authors.lastname: Brunham
mesh_terms: D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes; D002460:Cell Line; D002690:Chlamydia Infections / Q000276:immunology*; D023502:Chlamydia muridarum / Q000276:immunology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000382:microbiology; D000939:Epitopes / Q000276:immunology*; D005786:Gene Expression Regulation / Q000502:physiology; D007111:Immunity, Cellular; D007371:Interferon-gamma; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D016207:Cytokines; D000939:Epitopes; C410161:PmpG protein, Chlamydia trachomatis; D007371:Interferon-gamma