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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.