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Infection and Immunity, February 2009, p. 896-903, Vol. 77, No. 2
0019-9567/09/$08.00+0     doi:10.1128/IAI.00769-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Immunodominance in Mouse and Human CD4+ T-Cell Responses Specific for the Bordetella pertussis Virulence Factor P.69 Pertactin{triangledown}

Rachel M. Stenger,1* Martien C. M. Poelen,1 Ed E. Moret,2 Betsy Kuipers,1 Sven C. M. Bruijns,1 Peter Hoogerhout,1 Marcel Hijnen,3,{dagger} Audrey J. King,3 Frits R. Mooi,3 Claire J. P. Boog,1 and Cécile A. C. M. van Els1

Laboratory of Vaccine Research, Netherlands Vaccine Institute,1 Laboratory of Vaccine Preventable Diseases, National Institute for Public Health and the Environment, Bilthoven,3 Medicinal Chemistry and Chemical Biology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands2

Received 19 June 2008/ Returned for modification 18 August 2008/ Accepted 27 October 2008

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-Ad-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.


* Corresponding author. Mailing address: Laboratory of Vaccine Research, Netherlands Vaccine Institute, Antonie van Leeuwenhoeklaan 11, 3721 MA Bilthoven, The Netherlands. Phone: 0031-30-2743999. Fax: 0031-30-2744429. E-mail: Rachel.Stenger{at}nvi-vaccin.nl

{triangledown} Published ahead of print on 17 November 2008.

Editor: B. A. McCormick

{dagger} Present address: Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Australia.


Infection and Immunity, February 2009, p. 896-903, Vol. 77, No. 2
0019-9567/09/$08.00+0     doi:10.1128/IAI.00769-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.