Control of cross-presentation during dendritic cell maturation.
The initiation of most cytotoxic immune responses requires MHC class I-restricted presentation of internalized antigens to CD8(+) T lymphocytes, a process called cross-presentation. In dendritic cells (DC), the only antigen-presenting cells that activate naive T cells, cross-presentation is particularly efficient after internalization of opsonized antigens or immune complexes, which are cross-presented through a proteasome- and transporter associated with antigen processing (TAP)-dependent MHC class I antigen presentation pathway. We now show that FcgammaR-mediated cross-presentation is tightly regulated during DC maturation. Cross-presentation increases soon after activation by lipopolysaccharides, and it is then inhibited in fully mature cells. The initial induction of cross-presentation results from an increase of both antigen internalization and delivery to the cytosol, and from a slight rise in the activity of the proteasome and TAP. The subsequent block of cross-presentation in mature DC is a consequence of the selective down-modulation of antigen internalization and cytosolic delivery, while proteasome and TAP activities continue to rise. Therefore, FcgammaR-mediated cross-presentation is regulated during DC maturation by the selective control of antigen internalization and transport to the cytosol.
Gil-Torregrosa
Beatriz C
BC
U520 INSERM, Institut Curie, Paris, France.
Lennon-Duménil
Ana Maria
AM
Kessler
Benedikt
B
Guermonprez
Pierre
P
Ploegh
Hidde L
HL
Fruci
Doriana
D
van Endert
Peter
P
Amigorena
Sebastian
S
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; D002454:Cell Differentiation / Q000276:immunology*; D003546:Cysteine Endopeptidases / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D004527:Egg Proteins / Q000276:immunology; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D016130:Immunophenotyping; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009097:Multienzyme Complexes / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments; D046988:Proteasome Endopeptidase Complex
D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D000936:Antigen-Antibody Complex; D004527:Egg Proteins; D015395:Histocompatibility Antigens Class I; D009097:Multienzyme Complexes; C110366:OVA-8; D010446:Peptide Fragments; C489516:Tap2 protein, mouse; D010047:Ovalbumin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex