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Generation of Human Alloantigen-specific T Cells from Peripheral Blood
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Antigen kinetics determines immune reactivity

Pål Johansen1, Tazio Storni, Lorna Rettig

  • 1Unit Experimental Immunotherapy, Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, CH-8091 Zurich, Switzerland.

Proceedings of the National Academy of Sciences of the United States of America
|March 26, 2008
PubMed

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.

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