Antigen kinetics determines immune reactivity

被引:144
作者
Johansen, Pal [1 ]
Storni, Tazio [1 ]
Rettig, Lorna [1 ]
Qiu, Zhiyong [2 ]
Der-Sarkissian, Ani [2 ]
Smith, Kent A. [2 ]
Manolova, Vania [3 ]
Lang, Karl S. [4 ]
Senti, Gabriela [1 ,5 ]
Muellhaupt, Beat [6 ]
Gerlach, Tillman [6 ]
Speck, Roberto F. [7 ]
Bot, Adrian [2 ]
Kuendig, Thomas M. [1 ]
机构
[1] Univ Zurich Hosp, Dept Dermatol, Unit Expt Immunotherapy, CH-8091 Zurich, Switzerland
[2] MannKind Corp, Valencia, CA 91355 USA
[3] Cytos Biotechnol, CH-8952 Schlieren, Switzerland
[4] Univ Zurich Hosp, Inst Expt Immunol, CH-8091 Zurich, Switzerland
[5] Univ Zurich Hosp, Clin Trials Ctr, CH-8091 Zurich, Switzerland
[6] Univ Zurich Hosp, Dept Gastroenterol & Hepatol, CH-8091 Zurich, Switzerland
[7] Univ Zurich Hosp, Div Infect Dis & Hosp Epidemiol, CH-8091 Zurich, Switzerland
关键词
antigen presentation; antiviral immunity; CD8 T cell responses; tumor vaccine;
D O I
10.1073/pnas.0706296105
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 CD8T 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.
引用
收藏
页码:5189 / 5194
页数:6
相关论文
共 51 条
[1]   A structure-based approach to designing non-natural peptides that can activate anti-melanoma cytotoxic T cells [J].
Ayyoub, M ;
Mazarguil, H ;
Monsarrat, B ;
Van den Eynde, B ;
Gairin, JE .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (15) :10227-10234
[2]   INDUCTION OF PROTECTIVE CYTOTOXIC T-CELLS WITH VIRAL-PROTEINS [J].
BACHMANN, MF ;
KUNDIG, TM ;
FREER, G ;
LI, Y ;
KANG, CY ;
BISHOP, DH ;
HENGARTNER, H ;
ZINKERNAGEL, RM .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1994, 24 (09) :2228-2236
[3]   THE INFLUENCE OF ANTIGEN ORGANIZATION ON B-CELL RESPONSIVENESS [J].
BACHMANN, MF ;
ROHRER, UH ;
KUNDIG, TM ;
BURKI, K ;
HENGARTNER, H ;
ZINKERNAGEL, RM .
SCIENCE, 1993, 262 (5138) :1448-1451
[4]   QUANTIFICATION OF LYMPHOCYTIC CHORIOMENINGITIS VIRUS WITH AN IMMUNOLOGICAL FOCUS ASSAY IN 24-WELL OR 96-WELL PLATES [J].
BATTEGAY, M ;
COOPER, S ;
ALTHAGE, A ;
BANZIGER, J ;
HENGARTNER, H ;
ZINKERNAGEL, RM .
JOURNAL OF VIROLOGICAL METHODS, 1991, 33 (1-2) :191-198
[5]  
BINDER D, 1991, J IMMUNOL, V146, P4301
[6]   Increased immunogenicity of an anchor-modified tumor-associated antigen is due to the enhanced stability of the peptide/MHC complex: Implications for vaccine design [J].
Borbulevych, OY ;
Baxter, TK ;
Yu, ZY ;
Restifo, NP ;
Baker, BM .
JOURNAL OF IMMUNOLOGY, 2005, 174 (08) :4812-4820
[7]   Dynamics of CD8+ T cell priming by dendritic cells in intact lymph nodes [J].
Bousso, P ;
Robey, E .
NATURE IMMUNOLOGY, 2003, 4 (06) :579-585
[8]  
Brinckerhoff LH, 1999, INT J CANCER, V83, P326, DOI 10.1002/(SICI)1097-0215(19991029)83:3<326::AID-IJC7>3.0.CO
[9]  
2-X
[10]   Structural and kinetic basis for heightened immunogenicity of T cell vaccines [J].
Chen, JL ;
Stewart-Jones, G ;
Bossi, G ;
Lissin, NM ;
Wooldridge, L ;
Choi, EML ;
Held, G ;
Dunbar, PR ;
Esnouf, RM ;
Sami, M ;
Boulter, JM ;
Rizkallah, P ;
Renner, C ;
Sewell, A ;
van der Merwe, PA ;
Jakobsen, BK ;
Griffiths, G ;
Jones, EY ;
Cerundolo, V .
JOURNAL OF EXPERIMENTAL MEDICINE, 2005, 201 (08) :1243-1255