The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/1/371/ $5.00
The Journal of Experimental Medicine, Volume 189, Number 2, January 18, 1999 371-380

Articles

Fc{gamma} Receptor–mediated Induction of Dendritic Cell Maturation and Major Histocompatibility Complex Class I–restricted Antigen Presentation after Immune Complex Internalization

Armelle Regnault*, Danielle Lankar*, Valérie Lacabanne*, Ana Rodriguez*, Clotilde Théry*, Maria Rescigno{ddagger}, Takashi Saito||, Sjef Verbeek§, Christian Bonnerot*, Paola Ricciardi-Castagnoli{ddagger}, and Sebastian Amigorena*

From * Institut National de la Santé et de la Recherche Médicale CJF 95-01, Institut Curie, Section Recherche, 75005 Paris, France; the {ddagger} Second University of Milan, Department of Biotechnology and Biological Sciences, 20126 Milan, Italy; the § Department of Immunology, University Hospital, G04.614, 3584 CX, Utrecht, The Netherlands; and the || Division of Molecular Genetics, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, Japan

Dendritic cells (DCs) express several receptors for the Fc portion of immunoglobulin (Ig)G (Fc{gamma}R), which mediate internalization of antigen–IgG complexes (immune complexes, ICs) and promote efficient major histocompatibility complex (MHC) class II–restricted antigen presentation. We now show that Fc{gamma}Rs have two additional specific attributes in murine DCs: the induction of DC maturation and the promotion of efficient MHC class I–restricted presentation of peptides from exogenous, IgG-complexed antigens. Both Fc{gamma}R functions require the Fc{gamma}R-associated {gamma} chain. Fc{gamma}R-mediated MHC class I–restricted antigen presentation is extremely sensitive and specific to immature DCs. It requires proteasomal degradation and is dependent on functional peptide transporter associated with antigen processing, TAP1-TAP2. By promoting DC maturation and presentation on both MHC class I and II molecules, ICs should efficiently sensitize DCs for priming of both CD4+ helper and CD8+ cytotoxic T lymphocytes in vivo.

Key Words: Fc receptors • dendritic cells • antigen presentation • immune complexes • cross-priming

Address correspondence to Sebastian Amigorena, Institut Curie, 12 rue Lhomond, 75005 Paris, France. Phone: 33-1-42-34-63-89; Fax: 33-1-42-34-63-82; E-mail: sebas{at}curie.fr

Abbreviations used: BM-DC, bone marrow–derived DC; CHX, cycloheximide; DC, dendritic cell; Fc{gamma}R-ct{gamma}, chimeric receptor composed of the lumenal and transmembrane domains of Fc{gamma}RII and the cytoplasmic tail of the {gamma} chain; HEL, hen egg lysozyme; IC, immune complex; ITAM, immunoreceptor tyrosine-based activation motif; LLnL, aldehyde N-acetyl-Leu-L-Leu-L-norleucinal; OVA-IC, OVA-containing IC; PTK, protein tyrosine kinase; TAP, transporter associated with antigen processing; wt, wild-type.


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