title: Immunodominance in mouse and human CD4+ T-cell responses specific for the Bordetella pertussis virulence factor P.69 pertactin.
abstract: P.69 pertactin (P.69 Prn), an adhesion molecule from the causative agent of pertussis, Bordetella pertussis, is present in cellular and most acellular vaccines that are currently used worldwide. Although both humoral immunity and cellular immunity directed against P.69 Prn have been implicated in protective immune mechanisms, the identities of CD4(+) T-cell epitopes on the P.69 Prn protein remain unknown. Here, a single I-A(d)-restricted B. pertussis conserved CD4(+) T-cell epitope at the N terminus of P.69 Prn was identified by using a BALB/c T-cell hybridoma. The epitope appeared immunodominant among four other minor strain-conserved P.69 Prn epitopes recognized after vaccination and B. pertussis infection, and it was capable of evoking a Th1/Th17-type cytokine response. B. pertussis P.69 Prn immune splenocytes did not cross-react with natural variants of the epitope as present in Bordetella parapertussis and Bordetella bronchiseptica. Finally, it was found that the immunodominant P.69 Prn epitope is broadly recognized in the human population by CD4(+) T cells in an HLA-DQ-restricted manner. During B. pertussis infection, the epitope was associated with a Th1-type CD4(+) T-cell response. Hence, this novel P.69 Prn epitope is involved in CD4(+) T-cell immunity after B. pertussis vaccination and infection in mice and, more importantly, in humans. Thus, it may provide a useful tool for the evaluation of the type, magnitude, and maintenance of B. pertussis-specific CD4(+) T-cell mechanisms in preclinical and clinical vaccine studies.
authors.affiliation: Laboratory of Vaccine Research, Netherlands Vaccine Institute, Bilthoven. Rachel.Stenger@nvi-vaccin.nl
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Stenger
authors.forename: Martien C M
authors.initials: MC
authors.lastname: Poelen
authors.forename: Ed E
authors.initials: EE
authors.lastname: Moret
authors.forename: Betsy
authors.initials: B
authors.lastname: Kuipers
authors.forename: Sven C M
authors.initials: SC
authors.lastname: Bruijns
authors.forename: Peter
authors.initials: P
authors.lastname: Hoogerhout
authors.forename: Marcel
authors.initials: M
authors.lastname: Hijnen
authors.forename: Audrey J
authors.initials: AJ
authors.lastname: King
authors.forename: Frits R
authors.initials: FR
authors.lastname: Mooi
authors.forename: Claire J P
authors.initials: CJ
authors.lastname: Boog
authors.forename: Cécile A C M
authors.initials: CA
authors.lastname: van Els
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000276:immunology*; D001886:Bordetella pertussis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006683:HLA-DQ Antigens / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D013047:Specific Pathogen-Free Organisms; D010566:Virulence Factors, Bordetella / Q000737:chemistry / Q000276:immunology*; D014917:Whooping Cough / Q000276:immunology
chemical_list: D001425:Bacterial Outer Membrane Proteins; D016207:Cytokines; D006683:HLA-DQ Antigens; D016056:Immunodominant Epitopes; D010566:Virulence Factors, Bordetella; C068929:pertactin