Antigen targeting to dendritic cells allows the identification of a CD4 T-cell epitope within an immunodominant Trypanosoma cruzi antigen

Eline V Rampazo; Kelly N S Amorim; Marcio M Yamamoto; Raquel Hoffmann Panatieri; Mauricio M Rodrigues; Silvia B Boscardin

doi:10.1371/journal.pone.0117778

Antigen targeting to dendritic cells allows the identification of a CD4 T-cell epitope within an immunodominant Trypanosoma cruzi antigen

PLoS One. 2015 Feb 13;10(2):e0117778. doi: 10.1371/journal.pone.0117778. eCollection 2015.

Authors

Eline V Rampazo¹, Kelly N S Amorim¹, Marcio M Yamamoto¹, Raquel Hoffmann Panatieri¹, Mauricio M Rodrigues², Silvia B Boscardin³

Affiliations

¹ Laboratory of Antigen Targeting to Dendritic Cells, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
² CTCMol, Federal University of São Paulo, São Paulo, Brazil; National Institute for Science and Technology in Vaccines, Belo Horizonte, Brazil.
³ Laboratory of Antigen Targeting to Dendritic Cells, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil; National Institute for Science and Technology in Vaccines, Belo Horizonte, Brazil.

Abstract

Targeting antigens to dendritic cells (DCs) by using hybrid monoclonal antibodies (mAbs) directed against DC receptors is known to improve activation and support long-lasting T cell responses. In the present work, we used the mAb αDEC205 fused to the Trypanosoma cruzi amastigote surface protein 2 (ASP-2) to identify a region of this protein recognized by specific T cells. The hybrid αDEC-ASP2 mAb was successfully generated and preserved its ability to bind the DEC205 receptor. Immunization of BALB/c mice with the recombinant mAb in the presence of polyriboinosinic: polyribocytidylic acid (poly (I:C)) specifically enhanced the number of IFN-γ producing cells and CD4+ T cell proliferation when compared to mice immunized with a mAb without receptor affinity or with the non-targeted ASP-2 protein. The strong immune response induced in mice immunized with the hybrid αDEC-ASP2 mAb allowed us to identify an ASP-2-specific CD4+ T cell epitope recognized by the BALB/c MHCII haplotype. We conclude that targeting parasite antigens to DCs is a useful strategy to enhance T cell mediated immune responses facilitating the identification of new T-cell epitopes.

Publication types

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

MeSH terms

Animals
Antibodies, Monoclonal / genetics
Antibodies, Monoclonal / immunology
Antibodies, Monoclonal / metabolism
Antibody Formation
Antigens, Protozoan / chemistry
Antigens, Protozoan / genetics
Antigens, Protozoan / immunology*
CD4-Positive T-Lymphocytes / immunology*
CD4-Positive T-Lymphocytes / metabolism
Chagas Disease / immunology
Chagas Disease / metabolism
Dendritic Cells / immunology*
Dendritic Cells / metabolism
Disease Models, Animal
Epitopes, T-Lymphocyte / immunology*
Female
HEK293 Cells
Humans
Immunization
Immunodominant Epitopes / immunology*
Mice
Neuraminidase / genetics
Neuraminidase / immunology
Peptides / immunology
Protein Binding / immunology
Recombinant Fusion Proteins / genetics
Recombinant Fusion Proteins / immunology
Recombinant Fusion Proteins / metabolism
Trypanosoma cruzi / immunology*

Substances

Antibodies, Monoclonal
Antigens, Protozoan
Epitopes, T-Lymphocyte
Immunodominant Epitopes
Peptides
Recombinant Fusion Proteins
ASP-2 protein, Trypanosoma cruzi
Neuraminidase

Grants and funding

This research was supported by the Brazilian National Research Council (CNPq)/National Institutes of Science and Technology in Vaccines (INCTV, 15203*12), Sao Paulo State Research Funding Agency (FAPESP, 2007/08648-9) and BNP-Paribas Bank. E.V. Rampazo, K.N.S. Amorim and R.H. Panatieri received fellowships from CNPq. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors acknowledge that partial funding for this study was provided by the commercial source BNP-Paribas Bank. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.