The geometry of synthetic peptide-based immunogens affects the efficiency of T cell stimulation by professional antigen-presenting cells

被引:25
作者
Fitzmaurice, CJ
Brown, LE
Kronin, V
Jackson, DC [1 ]
机构
[1] Univ Melbourne, Dept Microbiol & Immunol, Cooperat Res Ctr Vaccine Technol, Parkville, Vic 3052, Australia
[2] Walter & Eliza Hall Inst Med Res, Parkville, Vic 3052, Australia
关键词
antigen presentation; dendritic cells; epitope; synthetic peptide; vaccine;
D O I
10.1093/intimm/12.4.527
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
In the pathway leading to antibody production there are two points at which CD4(+) T-h cells need to be recruited. The first of these is priming of T cells by their interaction with dendritic cells (DC) bearing antigen presented on MHC class II molecules and the second is the collaborative interaction of these primed T cells with B cells presenting the same antigen. We have previously shown that the configuration of T and B cell determinants within synthetic peptide immunogens can greatly influence the amount of immunogen required to produce an antibody response. Here we investigate whether the difference in potency of different immunogens is related to their ability to be presented by either DC or B cells. We show that determinants in a branched configuration, which are the most efficient at eliciting antibody in vivo, are presented to T cell clones by splenic CD8(-) DC 10-fold more efficiently than the corresponding determinants in a tandem linear arrangement. B cells also showed preferential presentation of branched immunogens to one T cell clone but in contrast to DC, not to a second T cell clone, indicating differences between the two antigen-presenting cell types. We also show that branched immunogens have a greater stability in serum compared to linear peptides, which may further enhance the differences in their in vivo potency.
引用
收藏
页码:527 / 535
页数:9
相关论文
共 33 条
[21]   THE EFFECT OF ORIENTATION OF EPITOPES ON THE IMMUNOGENICITY OF CHIMERIC SYNTHETIC PEPTIDES REPRESENTING MEASLES-VIRUS PROTEIN SEQUENCES [J].
PARTIDOS, C ;
STANLEY, C ;
STEWARD, M .
MOLECULAR IMMUNOLOGY, 1992, 29 (05) :651-658
[22]   ANTIGEN PRESENTATION MEDIATED BY RECYCLING OF SURFACE HLA-DR MOLECULES [J].
PINET, V ;
VERGELLI, M ;
MARTIN, R ;
BAKKE, O ;
LONG, EO .
NATURE, 1995, 375 (6532) :603-606
[23]  
PINET V, 1994, J IMMUNOL, V152, P4852
[24]   DENDRITIC CELLS USE MACROPINOCYTOSIS AND THE MANNOSE RECEPTOR TO CONCENTRATE MACROMOLECULES IN THE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II COMPARTMENT - DOWN-REGULATION BY CYTOKINES AND BACTERIAL PRODUCTS [J].
SALLUSTO, F ;
CELLA, M ;
DANIELI, C ;
LANZAVECCHIA, A .
JOURNAL OF EXPERIMENTAL MEDICINE, 1995, 182 (02) :389-400
[25]   Efficient Presentation of Soluble Antigen by Cultured Human Dendritic Cells Is Maintained by Granulocyte/Macrophage Colony-stimulating Factor Plus Interleukin 4 and Downregulated by Tumor Necrosis Factor α [J].
Sallusto, Federica ;
Lanzavecchia, Antonio .
JOURNAL OF IMMUNOLOGY, 2018, 200 (03) :887-896
[26]  
SCHOOFS PG, 1988, J IMMUNOL, V140, P611
[27]   CODOMINANT AND RECIPROCAL T-HELPER CELL-ACTIVITY OF EPITOPIC SEQUENCES AND FORMATION OF JUNCTIONAL B-CELL DETERMINANTS IN SYNTHETIC T-B CHIMERIC IMMUNOGENS [J].
SHARMA, P ;
KUMAR, A ;
BATNI, S ;
CHAUHAN, VS .
VACCINE, 1993, 11 (13) :1321-1326
[28]  
Steinman RM., 2003, ANNU REV IMMUNOL, V9, P271
[29]   A subclass of dendritic cells kills CD4 T cells via Fas Fas-ligand-induced apoptosis [J].
Suss, G ;
Shortman, K .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 183 (04) :1789-1796
[30]  
Viner NJ, 1996, J IMMUNOL, V156, P2365