title: Robust T-cell stimulation by Epstein-Barr virus-transformed B cells after antigen targeting to DEC-205.
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-205–targeted 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-205–targeted 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-205–targeted 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.
authors.affiliation: Departments of Viral Immunobiology and Neuroinflammation, Institute of Experimental Immunology, University of Zürich, Zürich, Switzerland.
authors.forename: Carol S
authors.initials: CS
authors.lastname: Leung
authors.forename: Michael A
authors.initials: MA
authors.lastname: Maurer
authors.forename: Sonja
authors.initials: S
authors.lastname: Meixlsperger
authors.forename: Anne
authors.initials: A
authors.lastname: Lippmann
authors.forename: Cheolho
authors.initials: C
authors.lastname: Cheong
authors.forename: Jianmin
authors.initials: J
authors.lastname: Zuo
authors.forename: Tracey A
authors.initials: TA
authors.lastname: Haigh
authors.forename: Graham S
authors.initials: GS
authors.lastname: Taylor
authors.forename: Christian
authors.initials: C
authors.lastname: Münz
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000502:physiology; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000502:physiology; D004854:Herpesvirus 4, Human / Q000276:immunology / Q000502:physiology*; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015778:Minor Histocompatibility Antigens; D058990:Molecular Targeted Therapy; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D014611:Vaccination / Q000379:methods
chemical_list: D015703:Antigens, CD; C093569:DEC-205 receptor; D037181:Lectins, C-Type; D015778:Minor Histocompatibility Antigens; D011947:Receptors, Antigen, B-Cell; D011956:Receptors, Cell Surface