Induction of vigorous helper and cytotoxic T cell as well as B cell responses by dendritic cells expressing a modified antigen targeting receptor-mediated internalization pathway.
Efficient Ag presentation is essential to induce effective cellular and humoral immune responses. Thus, one central goal of current immunotherapy and vaccine development is to enhance Ag presentation to induce potent and broad immune responses. Here, a novel Ag presentation strategy is developed by transducing dendritic cells (DCs) to produce an Ag for presentation as an exogenous Ag to efficiently induce both humoral and cellular immunity. The principle of this strategy is illustrated by genetically modifying DCs to secrete a model hepatitis B virus Ag fused with a cell-binding domain and to process the fusion Ag as an exogenous Ag after receptor-mediated internalization for MHC class I and II presentation. Vigorous Ag-specific CD4(+) helper and CD8(+) cytotoxic T cell, as well as B cell, responses were induced by the transduced DCs in mouse models. Thus, this novel strategy uses a receptor-mediated internalization process to efficiently induce all arms of the adaptive immunity and may provide a powerful means to develop potent vaccines and immunotherapies.
You
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Center for Cell and Gene Therapy, Department of Molecular and Human Genetics, and Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Huang
X F
XF
Hester
J
J
Rollins
L
L
Rooney
C
C
Chen
S Y
SY
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics*; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000637:transplantation; D005822:Genetic Vectors / Q000008:administration & dosage / Q000276:immunology; D006512:Hepatitis B Core Antigens / Q000235:genetics / Q000276:immunology; D006513:Hepatitis B e Antigens / Q000235:genetics / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000502:physiology; D016219:Immunotherapy, Adoptive / Q000379:methods; D007274:Injections, Intraperitoneal; D008213:Lymphocyte Activation / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009368:Neoplasm Transplantation; D019251:Nucleocapsid / Q000235:genetics / Q000276:immunology; D017452:Receptors, IgG / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000096:biosynthesis / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D012878:Skin Neoplasms / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D006512:Hepatitis B Core Antigens; D006513:Hepatitis B e Antigens; D000949:Histocompatibility Antigens Class II; D007141:Immunoglobulin Fc Fragments; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins