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Blood ; 121(9): 1584-94, 2013 Feb 28.
Article in English | MEDLINE | ID: mdl-23297134

ABSTRACT

DEC-205 is a type I transmembrane multilectin receptor that is predominantly expressed on dendritic cells (DCs). Therefore, previous studies primarily focused on processing of DEC-205­targeted antigens by this potent antigen presenting cell type. Here we show that Epstein-Barr virus (EBV) transformed lymphoblastoid B-cell lines (LCLs) not only express DEC-205 at similar levels to DCs, but also efficiently present targeted EBV nuclear antigen 1 (EBNA1) and EBV-latent membrane protein 1 (LMP1) to EBNA1- and LMP1-specific CD4+ and CD8+ T-cell clones in vitro. Targeting of antigens to DEC-205 on B cells led to more efficient MHC class II than I loading, and stimulated T cells more efficiently than targeting to DEC-205 on DCs. Although LCLs internalized DEC-205­targeted antigens less efficiently than DCs, they retained them for longer time periods and delivered them to endosomal compartments that receive also B-cell receptor targeted proteins. This could facilitate prolonged T-cell stimulation and efficient MHC class II loading, and, indeed, CD4+ T-cell expansion by DEC-205­targeted vaccination was significantly compromised in B-cell deficient mice. These studies suggest that B cells, activated by virus transformation or other means, can contribute to T-cell stimulation after DEC-205 targeting of antigens during vaccination.


Subject(s)
Antigens, CD/metabolism , B-Lymphocytes/immunology , B-Lymphocytes/virology , Dendritic Cells/immunology , Herpesvirus 4, Human/physiology , Lectins, C-Type/metabolism , Receptors, Cell Surface/metabolism , T-Lymphocytes/immunology , Animals , Antigen Presentation/physiology , Antigens, CD/immunology , B-Lymphocytes/metabolism , Cell Line, Transformed , Cell Transformation, Viral/immunology , Cells, Cultured , Dendritic Cells/physiology , Herpesvirus 4, Human/immunology , Lectins, C-Type/immunology , Lymphocyte Activation/immunology , Mice , Mice, Inbred C57BL , Mice, Transgenic , Minor Histocompatibility Antigens , Molecular Targeted Therapy , Receptors, Antigen, B-Cell/immunology , Receptors, Antigen, B-Cell/metabolism , Receptors, Cell Surface/immunology , T-Lymphocytes/metabolism , T-Lymphocytes/physiology , Vaccination/methods
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