title: Antigen targeting to dendritic cells allows the identification of a CD4 T-cell epitope within an immunodominant Trypanosoma cruzi antigen.
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.
authors: Laboratory of Antigen Targeting to Dendritic Cells, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors: Eline V
authors: EV
authors: Rampazo
authors: Laboratory of Antigen Targeting to Dendritic Cells, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors: Kelly N S
authors: KN
authors: Amorim
authors: Laboratory of Antigen Targeting to Dendritic Cells, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors: Marcio M
authors: MM
authors: Yamamoto
authors: Laboratory of Antigen Targeting to Dendritic Cells, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
authors: Raquel Hoffmann
authors: RH
authors: Panatieri
authors: CTCMol, Federal University of São Paulo, São Paulo, Brazil; National Institute for Science and Technology in Vaccines, Belo Horizonte, Brazil.
authors: Mauricio M
authors: MM
authors: Rodrigues
authors: 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.
authors: Silvia B
authors: SB
authors: Boscardin
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000917:Antibody Formation; D000953:Antigens, Protozoan / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014355:Chagas Disease / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D007114:Immunization; D016056:Immunodominant Epitopes / Q000276:immunology*; D051379:Mice; D009439:Neuraminidase / Q000235:genetics / Q000276:immunology; D010455:Peptides / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D000953:Antigens, Protozoan; D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes; D010455:Peptides; D011993:Recombinant Fusion Proteins; C493236:ASP-2 protein, Trypanosoma cruzi; D009439:Neuraminidase