FcRn regulates antigen presentation in dendritic cells downstream of DEC205-targeted vaccines.

Journal

NPJ vaccines
ISSN: 2059-0105
Titre abrégé: NPJ Vaccines
Pays: England
ID NLM: 101699863

Informations de publication

Date de publication:
09 Apr 2024
Historique:
received: 28 07 2023
accepted: 29 02 2024
medline: 10 4 2024
pubmed: 10 4 2024
entrez: 9 4 2024
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41541-024-00854-8 PMID: 38594284
pubmed: 38594284
doi: 10.1038/s41541-024-00854-8
pii: 10.1038/s41541-024-00854-8
doi:

Types de publication

Journal Article

Langues

eng

Pagination

76

Informations de copyright

© 2024. Crown.

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Auteurs

Christophe Macri (C)

Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, 30 Flemington Rd, Parkville, The University of Melbourne, Victoria, 3010, Australia.

Matthew Paxman (M)

Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, 30 Flemington Rd, Parkville, The University of Melbourne, Victoria, 3010, Australia.
ORCID: 0009-0000-5658-5747

Devi Jenika (D)

Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, 30 Flemington Rd, Parkville, The University of Melbourne, Victoria, 3010, Australia.

Xiao Peng Lin (XP)

Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, 30 Flemington Rd, Parkville, The University of Melbourne, Victoria, 3010, Australia.
ORCID: 0000-0003-1069-6948

Zahra Elahi (Z)

Department of Anatomy and Physiology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, Victoria, 3010, Australia.

Paul A Gleeson (PA)

Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, 30 Flemington Rd, Parkville, The University of Melbourne, Victoria, 3010, Australia.

Irina Caminschi (I)

Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria, 3010, Australia.
Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, 3800, Australia.

Mireille H Lahoud (MH)

Monash Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, 3800, Australia.
ORCID: 0000-0001-8472-6201

Jose A Villadangos (JA)

Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, 30 Flemington Rd, Parkville, The University of Melbourne, Victoria, 3010, Australia.
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria, 3010, Australia.

Justine D Mintern (JD)

Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, 30 Flemington Rd, Parkville, The University of Melbourne, Victoria, 3010, Australia. jmintern@unimelb.edu.au.
ORCID: 0000-0002-3797-8577

Classifications MeSH