Targeting viral antigens to CD11c on dendritic cells induces retrovirus-specific T cell responses

Asim Ejaz; Christoph G Ammann; Roland Werner; Georg Huber; Verena Oberhauser; Susanne Hörl; Simone Schimmer; Ulf Dittmer; Dorothee von Laer; Heribert Stoiber; Zoltán Bánki

doi:10.1371/journal.pone.0045102

Targeting viral antigens to CD11c on dendritic cells induces retrovirus-specific T cell responses

PLoS One. 2012;7(9):e45102. doi: 10.1371/journal.pone.0045102. Epub 2012 Sep 17.

Authors

Asim Ejaz¹, Christoph G Ammann, Roland Werner, Georg Huber, Verena Oberhauser, Susanne Hörl, Simone Schimmer, Ulf Dittmer, Dorothee von Laer, Heribert Stoiber, Zoltán Bánki

Affiliation

¹ Division of Virology, Innsbruck Medical University, Innsbruck, Austria.

Abstract

Dendritic cells (DC) represent the most potent antigen presenting cells and induce efficient cytotoxic T lymphocyte (CTL) responses against viral infections. Targeting antigens (Ag) to receptors on DCs is a promising strategy to enhance antitumor and antiviral immune responses induced by DCs. Here, we investigated the potential of CD11c-specific single-chain fragments (scFv) fused to an immunodominant peptide of Friend retrovirus for induction of virus-specific T cell responses by DCs. In vitro CD11c-specific scFv selectively targeted viral antigens to DCs and thereby significantly improved the activation of virus-specific T cells. In vaccination experiments DCs loaded with viral Ag targeted to CD11c provided improved rejection of FV-derived tumors and efficiently primed virus-specific CTL responses after virus challenge. Since the induction of strong virus-specific T cell responses is critical in viral infections, CD11c targeted protein vaccines might provide means to enhance the cellular immune response to prophylactic or therapeutic levels.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Animals
Antigens, Viral / chemistry
Antigens, Viral / immunology*
CD11c Antigen / immunology*
Cell Line, Tumor
Cell Proliferation
Dendritic Cells / immunology*
Female
Immunization
Immunodominant Epitopes / chemistry
Immunodominant Epitopes / immunology
Lymphocyte Activation / immunology
Mice
Mice, Inbred C57BL
Molecular Sequence Data
Ovalbumin / immunology
Recombinant Fusion Proteins / metabolism
Retroviridae / immunology*
Single-Chain Antibodies / chemistry
Single-Chain Antibodies / immunology
Species Specificity
Spleen / cytology
T-Lymphocytes, Cytotoxic / immunology*
T-Lymphocytes, Cytotoxic / virology*
env Gene Products, Human Immunodeficiency Virus / immunology
gag Gene Products, Human Immunodeficiency Virus / immunology

Substances

Antigens, Viral
CD11c Antigen
Immunodominant Epitopes
Recombinant Fusion Proteins
Single-Chain Antibodies
env Gene Products, Human Immunodeficiency Virus
gag Gene Products, Human Immunodeficiency Virus
Ovalbumin

Grants and funding

The authors are supported by grants of the Austrian Science Fund (FWF): P21508-B13 to ZB, the 6th frame work of the EU (DEC-VAC 2005-018685 to HS), and the Federal Government of Tyrol (Tiroler Wissenschaftsfonds TWF-2008-1-562 to HS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.