Targeting the nuclear antigen 1 of Epstein-Barr virus to the human endocytic receptor DEC-205 stimulates protective T-cell responses.
Dendritic cells (DCs) express many endocytic receptors that deliver antigens for major histocompatibility class (MHC) I and II presentation to CD8(+) and CD4(+) T cells, respectively. Here, we show that targeting Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) to one of them, the human multilectin DEC-205 receptor, in the presence of the DC maturation stimulus poly(I:C), expanded EBNA1-specific CD4(+) and CD8(+) memory T cells, and these lymphocytes could control the outgrowth of autologous EBV-infected B cells in vitro. In addition, using a novel mouse model with reconstituted human immune system components, we demonstrated that vaccination with alphaDEC-205-EBNA1 antibodies primed EBNA1-specific IFN-gamma-secreting T cells and also induced anti-EBNA1 antibodies in a subset of immunized mice. Because EBNA1 is the one EBV antigen that is expressed in all proliferating cells infected with this virus, our data suggest that DEC-205 targeting should be explored as a vaccination approach against symptomatic primary EBV infection and against EBV-associated malignancies.
Laboratory of Viral Immunobiology, Christopher H Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, NY 10065, USA.
Cagan
C
Gurer
Till
T
Strowig
Fabienne
F
Brilot
Maggi
M
Pack
Christine
C
Trumpfheller
Frida
F
Arrey
Chae Gyu
CG
Park
Ralph M
RM
Steinman
Christian
C
Münz
D000818:Animals; D000914:Antibodies, Viral; D015703:Antigens, CD / Q000276:immunology*; D001402:B-Lymphocytes / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000276:immunology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology*; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D037181:Lectins, C-Type / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination
D000914:Antibodies, Viral; D015703:Antigens, CD; C093569:DEC-205 receptor; D019309:Epstein-Barr Virus Nuclear Antigens; D037181:Lectins, C-Type; D015778:Minor Histocompatibility Antigens; D011956:Receptors, Cell Surface