Abstract
Chlamydia infections cause substantial morbidity worldwide and effective prevention will depend on a vaccine. Since Chlamydia immunity is T cell-mediated, a major impediment to developing a molecular vaccine has been the difficulty in identifying relevant T cell Ags. In this study, we used a combination of affinity chromatography and tandem mass spectrometry to identify 13 Chlamydia peptides among 331 self-peptides presented by MHC class II (I-A(b)) molecules from bone marrow-derived murine dendritic cells infected with Chlamydia muridarum. These MHC class II-bound peptides were recognized by Chlamydia-specific CD4 T cells harvested from immune mice and adoptive transfer of dendritic cells pulsed ex vivo with the peptides partially protected mice against intranasal and genital tract Chlamydia infection. The results provide evidence for lead vaccine candidates for a T cell-based subunit molecular vaccine against Chlamydia infection suitable for human study.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Antigens, Bacterial / isolation & purification*
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Antigens, Bacterial / metabolism
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Antigens, Bacterial / therapeutic use
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Antigens, Differentiation, T-Lymphocyte / isolation & purification*
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Antigens, Differentiation, T-Lymphocyte / metabolism
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Antigens, Differentiation, T-Lymphocyte / therapeutic use
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Cells, Cultured
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Chlamydia Infections / immunology
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Chlamydia Infections / metabolism
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Chlamydia Infections / prevention & control
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Chlamydia muridarum / immunology*
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Dendritic Cells / immunology
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Dendritic Cells / metabolism
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Dendritic Cells / transplantation
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Female
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H-2 Antigens / isolation & purification
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H-2 Antigens / metabolism
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HeLa Cells
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Histocompatibility Antigens Class II / isolation & purification
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Histocompatibility Antigens Class II / metabolism
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Histocompatibility Antigens Class II / therapeutic use
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Humans
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Intracellular Fluid / chemistry
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Intracellular Fluid / immunology*
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Intracellular Fluid / microbiology*
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Mice
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Mice, Inbred C57BL
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Molecular Sequence Data
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Peptides / isolation & purification
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Peptides / metabolism
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Peptides / therapeutic use
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Protein Binding / immunology
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Proteome / immunology*
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Proteome / isolation & purification
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Proteome / metabolism
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Tandem Mass Spectrometry
Substances
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Antigens, Bacterial
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Antigens, Differentiation, T-Lymphocyte
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H-2 Antigens
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Histocompatibility Antigens Class II
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Peptides
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Proteome