title: 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.
authors: Unit Experimental Immunotherapy, Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, CH-8091 Zurich, Switzerland.
authors: Pål
authors: P
authors: Johansen
authors: Tazio
authors: T
authors: Storni
authors: Lorna
authors: L
authors: Rettig
authors: Zhiyong
authors: Z
authors: Qiu
authors: Ani
authors: A
authors: Der-Sarkissian
authors: Kent A
authors: KA
authors: Smith
authors: Vania
authors: V
authors: Manolova
authors: Karl S
authors: KS
authors: Lang
authors: Gabriela
authors: G
authors: Senti
authors: Beat
authors: B
authors: Müllhaupt
authors: Tilman
authors: T
authors: Gerlach
authors: Roberto F
authors: RF
authors: Speck
authors: Adrian
authors: A
authors: Bot
authors: Thomas M
authors: TM
authors: Kündig
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology*; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D007376:Interleukin-2 / Q000096:biosynthesis; D007700:Kinetics; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D014765:Viral Vaccines / Q000276:immunology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000941:Antigens; D007376:Interleukin-2; D014765:Viral Vaccines