gms | German Medical Science

10. Kongress für Infektionskrankheiten und Tropenmedizin (KIT 2010)

Deutsche Gesellschaft für Infektiologie,
Deutsche AIDS-Gesellschaft,
Deutsche Gesellschaft für Tropenmedizin und Internationale Gesundheit,
Paul-Ehrlich-Gesellschaft für Chemotherapie

23.06. - 26.06.2010, Köln

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The synthetic TLR2 agonist BPPcysMPEG leads to efficient cross-priming against co-administered and linked antigens

Der synthetische TLR2-Agonist BPPcysMPEG induziert eine effektive Immunität zytotoxischer Lymphozyten gegen gleichzeitig verabreichte oder gekoppelte Antigene

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  • C. K. Prajeeth - Hannover Medical School, Clinic for Immunology and Rheumatology, Hannover, Germany
  • A. C. Jirmo - Hannover Medical School, Clinic for Immunology and Rheumatology, Hannover, Germany
  • J. K. Krishnaswamy - Hannover Medical School, Clinic for Immunology and Rheumatology, Hannover, Germany
  • T. Ebensen - Helmholtz Centre for Infection Research, Department of Vaccinology and Applied Microbiology, Braunschweig, Germany
  • C. A. Guzman - Helmholtz Centre for Infection Research, Department of Vaccinology and Applied Microbiology, Braunschweig, Germany
  • S. Weiss - Helmholtz Centre for Infection Research, Molecular Immunology, Braunschweig, Germany
  • H. Constabel - Hannover Medical School, Clinic for Immunology and Rheumatology, Hannover, Germany
  • R. E. Schmidt - Hannover Medical School, Clinic for Immunology and Rheumatology, Hannover, Germany
  • G. M. Behrens - Hannover Medical School, Clinic for Immunology and Rheumatology, Hannover, Germany

10. Kongress für Infektionskrankheiten und Tropenmedizin (KIT 2010). Köln, 23.-26.06.2010. Düsseldorf: German Medical Science GMS Publishing House; 2010. DocHIV 05-1

doi: 10.3205/10kit001, urn:nbn:de:0183-10kit0019

Published: June 2, 2010

© 2010 Prajeeth et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.

Outline

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The property of dendritic cells (DC) to generate effective cytotoxic T lymphocyte (CTL) responses is influenced by Toll-like Receptor (TLR) signalling. TLR ligands contain molecular signatures associated with pathogens, are being exploited as potential adjuvants, and have impact on the antigen processing and presentation by DC. We hypothesized that the TLR2/6 heterodimer agonist S-[2,3-bispalmitoyiloxy-(2R)-propyl]-R-cysteinyl-amido-monomethoxyl polyethylene glycol (BPP), a synthetic derivative of the Mycoplasma macrophage activating lipopeptide (MALP-2), is a potent adjuvant for cross-priming against cellular antigens. Systemic administration of BPP induced maturation of CD8α+DC and CD8α+DC in the spleen and resulted in enhanced cross-presentation of intravenously co-administered antigen in mice. In addition, administration of BPP and cell-associated OVA generated an effective CTL response against OVA in vivo in a CD4 T helper cell-dependent manner, but independent of IFN-α. Delivering antigenic peptides directly linked to BPP led to superior CTL immunity as compared to giving antigens and adjuvants admixed. In contrast to other TLR ligands, such as CpG, systemic activation of DC with BPP did not result in shut-down of antigen presentation by splenic DC subsets, although cross-priming against subsequently encountered antigens was reduced. Together our data provide evidence that BPP is a potent stimulus to generate CTL via cross-priming.