Antigen kinetics determines immune reactivity

P Johansen, T Storni, L Rettig, Z Qiu… - Proceedings of the …, 2008 - National Acad Sciences
P Johansen, T Storni, L Rettig, Z Qiu, A Der-Sarkissian, KA Smith, V Manolova, KS Lang…
Proceedings of the National Academy of Sciences, 2008National Acad Sciences
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 …
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.
National Acad Sciences