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FcRn regulates antigen presentation in dendritic cells downstream of DEC205-targeted vaccines.
Macri, Christophe; Paxman, Matthew; Jenika, Devi; Lin, Xiao Peng; Elahi, Zahra; Gleeson, Paul A; Caminschi, Irina; Lahoud, Mireille H; Villadangos, Jose A; Mintern, Justine D.
Afiliación
  • Macri C; Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, 30 Flemington Rd, Parkville, The University of Melbourne, Victoria, 3010, Australia.
  • Paxman M; Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, 30 Flemington Rd, Parkville, The University of Melbourne, Victoria, 3010, Australia.
  • Jenika D; Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, 30 Flemington Rd, Parkville, The University of Melbourne, Victoria, 3010, Australia.
  • Lin XP; Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, 30 Flemington Rd, Parkville, The University of Melbourne, Victoria, 3010, Australia.
  • Elahi Z; Department of Anatomy and Physiology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, Victoria, 3010, Australia.
  • Gleeson PA; Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, 30 Flemington Rd, Parkville, The University of Melbourne, Victoria, 3010, Australia.
  • Caminschi I; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria, 3010, Australia.
  • Lahoud MH; Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, 3800, Australia.
  • Villadangos JA; Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, 3800, Australia.
  • Mintern JD; Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, 30 Flemington Rd, Parkville, The University of Melbourne, Victoria, 3010, Australia.
NPJ Vaccines ; 9(1): 76, 2024 Apr 09.
Article en En | MEDLINE | ID: mdl-38594284
ABSTRACT
Dendritic cell (DC)-targeted vaccination is a new mode of antigen delivery that relies on the use of monoclonal antibodies (mAb) to target antigen to specific DC subsets. The neonatal Fc receptor (FcRn) is a non-classical Fc receptor that binds to immunoglobulin G (IgG) in acidified endosomes and controls its intracellular transport and recycling. FcRn is known to participate in the antigen presentation of immune complexes, however its contribution to DC-targeted vaccination has not previously been examined. Here we have investigated the role of FcRn in antigen presentation using antigen conjugated to IgG mAb which target specific DC receptors, including DEC205 and Clec9A expressed by the conventional DC 1 (cDC1) subset. We show that FcRn is expressed at high levels by cDC1, both at steady-state and following activation and plays a significant role in MHC I cross-presentation and MHC II presentation of antigens that are targeted to cDC1 via mAb specific for DEC205. This effect of FcRn is intrinsic to cDC1 and FcRn impacts the efficacy of anti-DEC205-mediated vaccination against B cell lymphoma. In contrast, FcRn does not impact presentation of antigens targeted to Clec9A and does not regulate presentation of cell-associated antigen. These data highlight a new and unique role of FcRn in controlling the immunogenicity of anti-DEC205-based vaccination, with consequences for exploiting this pathway to improve DC-targeted vaccine outcomes.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: NPJ Vaccines Año: 2024 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: NPJ Vaccines Año: 2024 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Reino Unido