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Antigen kinetics determines immune reactivity
- Johansen, Pål, Storni, Tazio, Rettig, Lorna, Qiu, Zhiyong, Der-Sarkissian, Ani, Smith, Kent A., Manolova, Vania, Lang, Karl S., Senti, Gabriela, Müllhaupt, Beat, Gerlach, Tilman, Speck, Roberto F., Bot, Adrian, Kündig, Thomas M.
- Proceedings of the National Academy of Sciences of the United States of America 2008 v.105 no.13 pp. 5189-5194
- CD8-positive T-lymphocytes, administered dose, antigens, immune response, mice, models, vaccination, vaccine development
- 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.