Control of cross-presentation during dendritic cell maturation.

Journal article

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.

Authors: Gil-Torregrosa, B; Lennon-Duménil, A; Kessler, B; Guermonprez, P; Ploegh, H

• Publication status: Published
• Journal: European journal of immunology
• Volume: 34
• Issue: 2
• Pages: 398-407
• Publication date: 2004-02-01
• DOI: 10.1002/eji.200324508
• EISSN: 1521-4141
• ISSN: 0014-2980
• Language: English
• Keywords: Immunophenotyping; Antigen Presentation; Cysteine Endopeptidases; Animals; Antigen-Antibody Complex; Cell Differentiation; Mice, Inbred C57BL; Egg Proteins; Flow Cytometry; Peptide Fragments; Mice, Knockout; Histocompatibility Antigens Class I; Mice; ATP-Binding Cassette Transporters; Dendritic Cells; Proteasome Endopeptidase Complex; Ovalbumin; Multienzyme Complexes