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Presentation of exogenous antigens on major histocompatibility complex (MHC) class I and MHC class II molecules is differentially regulated during dendritic cell maturation.

Delamarre L, Holcombe H, Mellman I - J. Exp. Med. (2003)

Bottom Line: Unlike MHC II, these events do not involve a marked redistribution of preexisting MHC I molecules from intracellular compartments to the DC surface.In contrast, formation of peptide-MHC I complexes from endogenous cytosolic antigens occurs even in unstimulated, immature DCs.Thus, the MHC I and MHC II pathways of antigen presentation are differentially regulated during DC maturation.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology and Section of Immunobiology, Ludwig Institute for Cancer Research, Yale University School of Medicine, New Haven, CT 06520-8002, USA.

ABSTRACT
During maturation, dendritic cells (DCs) regulate their capacity to process and present major histocompatibility complex (MHC) II-restricted antigens. Here we show that presentation of exogenous antigens by MHC I is also subject to developmental control, but in a fashion strikingly distinct from MHC II. Immature mouse bone marrow-derived DCs internalize soluble ovalbumin and sequester the antigen intracellularly until they receive an appropriate signal that induces cross presentation. At that time, peptides are generated in a proteasome-dependent fashion and used to form peptide-MHC I complexes that appear at the plasma membrane. Unlike MHC II, these events do not involve a marked redistribution of preexisting MHC I molecules from intracellular compartments to the DC surface. Moreover, out of nine stimuli well known to induce the phenotypic maturation of DCs and to promote MHC II presentation, only two (CD40 ligation, disruption of cell-cell contacts) activated cross presentation on MHC I. In contrast, formation of peptide-MHC I complexes from endogenous cytosolic antigens occurs even in unstimulated, immature DCs. Thus, the MHC I and MHC II pathways of antigen presentation are differentially regulated during DC maturation.

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Presentation of OVA by MHC I and MHC II is differentially regulated during DC maturation. Immature B6D2F1 DCs were pulsed with OVA 1mg/ml (or BSA as a control) for 2 h, washed, activated or not by addition of the indicated stimuli, and chased for 7 h before fixation and culture with CD4+ DO.11.10 T cells (specific for I-Ad/OVA). T cell responses were monitored at 24 h by measuring IL-2 release. One representative experiment out of >5 is shown.
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fig7: Presentation of OVA by MHC I and MHC II is differentially regulated during DC maturation. Immature B6D2F1 DCs were pulsed with OVA 1mg/ml (or BSA as a control) for 2 h, washed, activated or not by addition of the indicated stimuli, and chased for 7 h before fixation and culture with CD4+ DO.11.10 T cells (specific for I-Ad/OVA). T cell responses were monitored at 24 h by measuring IL-2 release. One representative experiment out of >5 is shown.

Mentions: OVA-pulsed DCs from B6D2F1 mice were cultured with OT.1 CD8+ T cells or the DO.11.10 CD4+ T cell hybridoma (specific for I-Ad /OVA complexes). As shown in Fig. 7, DCs stimulated with LPS alone or LPS together with cluster disruption exhibited comparable abilities to activate DO.11.10 CD4+ T cells. Thus, cluster disruption was not required for MHC II presentation. As mentioned earlier, our OVA contained detectable levels of endotoxins which induced DC maturation (unpublished data). These results for MHC II presentation contrast dramatically with those for MHC I cross presentation, as cross presentation of the same antigen under the same conditions was dependent on disrupting DC clusters before T cell assay (Fig. 4 A).


Presentation of exogenous antigens on major histocompatibility complex (MHC) class I and MHC class II molecules is differentially regulated during dendritic cell maturation.

Delamarre L, Holcombe H, Mellman I - J. Exp. Med. (2003)

Presentation of OVA by MHC I and MHC II is differentially regulated during DC maturation. Immature B6D2F1 DCs were pulsed with OVA 1mg/ml (or BSA as a control) for 2 h, washed, activated or not by addition of the indicated stimuli, and chased for 7 h before fixation and culture with CD4+ DO.11.10 T cells (specific for I-Ad/OVA). T cell responses were monitored at 24 h by measuring IL-2 release. One representative experiment out of >5 is shown.
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Related In: Results  -  Collection

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fig7: Presentation of OVA by MHC I and MHC II is differentially regulated during DC maturation. Immature B6D2F1 DCs were pulsed with OVA 1mg/ml (or BSA as a control) for 2 h, washed, activated or not by addition of the indicated stimuli, and chased for 7 h before fixation and culture with CD4+ DO.11.10 T cells (specific for I-Ad/OVA). T cell responses were monitored at 24 h by measuring IL-2 release. One representative experiment out of >5 is shown.
Mentions: OVA-pulsed DCs from B6D2F1 mice were cultured with OT.1 CD8+ T cells or the DO.11.10 CD4+ T cell hybridoma (specific for I-Ad /OVA complexes). As shown in Fig. 7, DCs stimulated with LPS alone or LPS together with cluster disruption exhibited comparable abilities to activate DO.11.10 CD4+ T cells. Thus, cluster disruption was not required for MHC II presentation. As mentioned earlier, our OVA contained detectable levels of endotoxins which induced DC maturation (unpublished data). These results for MHC II presentation contrast dramatically with those for MHC I cross presentation, as cross presentation of the same antigen under the same conditions was dependent on disrupting DC clusters before T cell assay (Fig. 4 A).

Bottom Line: Unlike MHC II, these events do not involve a marked redistribution of preexisting MHC I molecules from intracellular compartments to the DC surface.In contrast, formation of peptide-MHC I complexes from endogenous cytosolic antigens occurs even in unstimulated, immature DCs.Thus, the MHC I and MHC II pathways of antigen presentation are differentially regulated during DC maturation.

View Article: PubMed Central - PubMed

Affiliation: Department of Cell Biology and Section of Immunobiology, Ludwig Institute for Cancer Research, Yale University School of Medicine, New Haven, CT 06520-8002, USA.

ABSTRACT
During maturation, dendritic cells (DCs) regulate their capacity to process and present major histocompatibility complex (MHC) II-restricted antigens. Here we show that presentation of exogenous antigens by MHC I is also subject to developmental control, but in a fashion strikingly distinct from MHC II. Immature mouse bone marrow-derived DCs internalize soluble ovalbumin and sequester the antigen intracellularly until they receive an appropriate signal that induces cross presentation. At that time, peptides are generated in a proteasome-dependent fashion and used to form peptide-MHC I complexes that appear at the plasma membrane. Unlike MHC II, these events do not involve a marked redistribution of preexisting MHC I molecules from intracellular compartments to the DC surface. Moreover, out of nine stimuli well known to induce the phenotypic maturation of DCs and to promote MHC II presentation, only two (CD40 ligation, disruption of cell-cell contacts) activated cross presentation on MHC I. In contrast, formation of peptide-MHC I complexes from endogenous cytosolic antigens occurs even in unstimulated, immature DCs. Thus, the MHC I and MHC II pathways of antigen presentation are differentially regulated during DC maturation.

Show MeSH