Fcgamma receptor-mediated induction of dendritic cell maturation and major histocompatibility complex class I-restricted antigen presentation after immune complex internalization.
Dendritic cells (DCs) express several receptors for the Fc portion of immunoglobulin (Ig)G (FcgammaR), 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 FcgammaRs 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 FcgammaR functions require the FcgammaR-associated gamma chain. FcgammaR-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.
Regnault
A
A
Institut National de la Santé et de la Recherche Médicale CJF 95-01, Institut Curie, Section Recherche, 75005 Paris, France.
Lankar
D
D
Lacabanne
V
V
Rodriguez
A
A
Théry
C
C
Rescigno
M
M
Saito
T
T
Verbeek
S
S
Bonnerot
C
C
Ricciardi-Castagnoli
P
P
Amigorena
S
S
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000276:immunology; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000936:Antigen-Antibody Complex / Q000276:immunology*; D015703:Antigens, CD / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology; D003546:Cysteine Endopeptidases / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D005455:Fluorescent Antibody Technique; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009097:Multienzyme Complexes / Q000378:metabolism; D010047:Ovalbumin / Q000276:immunology; D046988:Proteasome Endopeptidase Complex; D017452:Receptors, IgG / Q000276:immunology*
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D000936:Antigen-Antibody Complex; D015703:Antigens, CD; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D009097:Multienzyme Complexes; D017452:Receptors, IgG; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse; C489516:Tap2 protein, mouse; C071692:TAP2 protein, human; D010047:Ovalbumin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex