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Bordetella pertussis proteins dominating the major histocompatibility complex class II-presented epitope repertoire in human monocyte-derived dendritic cells.
- Source :
-
Clinical and vaccine immunology : CVI [Clin Vaccine Immunol] 2014 May; Vol. 21 (5), pp. 641-50. Date of Electronic Publication: 2014 Mar 05. - Publication Year :
- 2014
-
Abstract
- Knowledge of naturally processed Bordetella pertussis-specific T cell epitopes may help to increase our understanding of the basis of cell-mediated immune mechanisms to control this reemerging pathogen. Here, we elucidate for the first time the dominant major histocompatibility complex (MHC) class II-presented B. pertussis CD4(+) T cell epitopes, expressed on human monocyte-derived dendritic cells (MDDC) after the processing of whole bacterial cells by use of a platform of immunoproteomics technology. Pertussis epitopes identified in the context of HLA-DR molecules were derived from two envelope proteins, i.e., putative periplasmic protein (PPP) and putative peptidoglycan-associated lipoprotein (PAL), and from two cytosolic proteins, i.e., 10-kDa chaperonin groES protein (groES) and adenylosuccinate synthetase (ASS). No epitopes were detectable from known virulence factors. CD4(+) T cell responsiveness in healthy adults against peptide pools representing epitope regions or full proteins confirmed the immunogenicity of PAL, PPP, groES, and ASS. Elevated lymphoproliferative activity to PPP, groES, and ASS in subjects within a year after the diagnosis of symptomatic pertussis suggested immunogenic exposure to these proteins during clinical infection. The PAL-, PPP-, groES-, and ASS-specific responses were associated with secretion of functional Th1 (tumor necrosis factor alpha [TNF-α] and gamma interferon [IFN-γ]) and Th2 (interleukin 5 [IL-5] and IL-13) cytokines. Relative paucity in the natural B. pertussis epitope display of MDDC, not dominated by epitopes from known protective antigens, can interfere with the effectiveness of immune recognition of B. pertussis. A more complete understanding of hallmarks in B. pertussis-specific immunity may advance the design of novel immunological assays and prevention strategies.
- Subjects :
- Adolescent
Adult
Aged
CD4-Positive T-Lymphocytes immunology
Cell Proliferation
Child
Cytokines metabolism
Female
Humans
Male
Middle Aged
Young Adult
Antigens, Bacterial immunology
Bacterial Proteins immunology
Bordetella pertussis immunology
Dendritic Cells immunology
Epitopes, T-Lymphocyte immunology
Immunodominant Epitopes immunology
Major Histocompatibility Complex immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1556-679X
- Volume :
- 21
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Clinical and vaccine immunology : CVI
- Publication Type :
- Academic Journal
- Accession number :
- 24599530
- Full Text :
- https://doi.org/10.1128/CVI.00665-13