Antigen kinetics determines immune reactivity.
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.
Johansen
Pål
P
Unit Experimental Immunotherapy, Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, CH-8091 Zurich, Switzerland.
Storni
Tazio
T
Rettig
Lorna
L
Qiu
Zhiyong
Z
Der-Sarkissian
Ani
A
Smith
Kent A
KA
Manolova
Vania
V
Lang
Karl S
KS
Senti
Gabriela
G
Müllhaupt
Beat
B
Gerlach
Tilman
T
Speck
Roberto F
RF
Bot
Adrian
A
Kündig
Thomas M
TM
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
D000941:Antigens; D007376:Interleukin-2; D014765:Viral Vaccines