Dendritic Cells Cross-Present Immunogenic Lentivector-Encoded Antigen from Transduced Cells to Prime Functional T Cell Immunity.
Recombinant lentiviral vectors (LVs) are highly effective vaccination vehicles that elicit protective T cell immunity in disease models. Dendritic cells (DCs) acquire antigen at sites of vaccination and migrate to draining lymph nodes, where they prime vaccine-specific T cells. The potency with which LVs activate CD8+T cell immunity has been attributed to the transduction of DCs at the immunization site and durable presentation of LV-encoded antigens. However, it is not known how LV-encoded antigens continue to be presented to T cells once directly transduced DCs have turned over. Here, we report that LV-encoded antigen is efficiently cross-presented by DCs in vitro. We have further exploited the temporal depletion of DCs in the murine CD11c.DTR (diphtheria toxin receptor) model to demonstrate that repopulating DCs that were absent at the time of immunization cross-present LV-encoded antigen to T cells in vivo. Indirect presentation of antigen from transduced cells by DCs is sufficient to prime functional effector T cells that control tumor growth. These data suggest that DCs cross-present immunogenic antigen from LV-transduced cells, thereby facilitating prolonged activation of T cells in the absence of circulating LV particles. These are findings that may impact on the future design of LV vaccination strategies.
Institute for Immunity and Transplantation, University College London, London NW3 2PF, UK.
Alastair
A
Hotblack
Institute for Immunity and Transplantation, University College London, London NW3 2PF, UK; Cancer Institute, University College London, London WC1E 6DD, UK.
Sara
S
Seshadri
Institute for Immunity and Transplantation, University College London, London NW3 2PF, UK; Cancer Institute, University College London, London WC1E 6DD, UK.
Lei
L
Zhang
Institute for Immunity and Transplantation, University College London, London NW3 2PF, UK; Cancer Institute, University College London, London WC1E 6DD, UK.
Sahar
S
Hamrang-Yousefi
Institute for Immunity and Transplantation, University College London, London NW3 2PF, UK; Cancer Institute, University College London, London WC1E 6DD, UK.
Ronjon
R
Chakraverty
Immunomodulation Group, Navarrabiomed-Fundaçion Miguel Servet, Calle de Irunlarrea 3, 31008 Pamplona, Spain.
David
D
Escors
Institute for Immunity and Transplantation, University College London, London NW3 2PF, UK; Cancer Institute, University College London, London WC1E 6DD, UK. Electronic address: c.bennett@ucl.ac.uk.
Clare L
CL
Bennett
D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000235:genetics / Q000276:immunology*; D015415:Biomarkers; D039521:CD11c Antigen / Q000378:metabolism; D019496:Cancer Vaccines / Q000276:immunology; D018920:Coculture Techniques; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005822:Genetic Vectors / Q000235:genetics; D066257:Heparin-binding EGF-like Growth Factor / Q000276:immunology; D007111:Immunity, Cellular; D016086:Lentivirus / Q000235:genetics; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D023421:Models, Animal; D009369:Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D014161:Transduction, Genetic; D014612:Vaccines / Q000235:genetics / Q000276:immunology
D000941:Antigens; D015415:Biomarkers; D039521:CD11c Antigen; D019496:Cancer Vaccines; D066257:Heparin-binding EGF-like Growth Factor; D014612:Vaccines
dendritic cells; lentivectors; vaccination