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Antigen kinetics determines immune reactivity.


ABSTRACT: A current paradigm in immunology is that the strength of T cell responses is governed by antigen dose, localization, and costimulatory signals. This study investigates the influence of antigen kinetics on CD8 T cell responses in mice. A fixed cumulative antigen dose was administered by different schedules to produce distinct dose-kinetics. Antigenic stimulation increasing exponentially over days was a stronger stimulus for CD8 T cells and antiviral immunity than a single dose or multiple dosing with daily equal doses. The same was observed for dendritic cell vaccination, with regard to T cell and anti-tumor responses, and for T cells stimulated in vitro. In conclusion, stimulation kinetics per se was shown to be a separate parameter of immunogenicity. These findings warrant a revision of current immunization models and have implications for vaccine development and immunotherapy.

SUBMITTER: Johansen P 

PROVIDER: S-EPMC2278203 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature

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Antigen kinetics determines immune reactivity.

Johansen Pål P   Storni Tazio T   Rettig Lorna L   Qiu Zhiyong Z   Der-Sarkissian Ani A   Smith Kent A KA   Manolova Vania V   Lang Karl S KS   Senti Gabriela G   Müllhaupt Beat B   Gerlach Tilman T   Speck Roberto F RF   Bot Adrian A   Kündig Thomas M TM  

Proceedings of the National Academy of Sciences of the United States of America 20080324 13


A current paradigm in immunology is that the strength of T cell responses is governed by antigen dose, localization, and costimulatory signals. This study investigates the influence of antigen kinetics on CD8 T cell responses in mice. A fixed cumulative antigen dose was administered by different schedules to produce distinct dose-kinetics. Antigenic stimulation increasing exponentially over days was a stronger stimulus for CD8 T cells and antiviral immunity than a single dose or multiple dosing  ...[more]

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