Published online 30 June 2003 doi:10.1084/jem.20021542
© Rockefeller University Press,
0022-1007/2003/7/111 $5.00
The Journal of Experimental Medicine, Volume 198, Number 1, 111-122
Presentation of Exogenous Antigens on Major Histocompatibility Complex (MHC) Class I and MHC Class II Molecules Is Differentially Regulated during Dendritic Cell Maturation
Lélia Delamarre,
Hilda Holcombe and
Ira Mellman
Department of Cell Biology and Section of Immunobiology, Ludwig Institute for Cancer Research, Yale University School of Medicine, New Haven, CT 06520
Address correspondence to I. Mellman, Department of Cell Biology and Section of Immunobiology, Ludwig Institute for Cancer Research, Yale University School of Medicine, 333 Cedar St., PO Box 208002, New Haven, CT 06520-8002. Phone: 203-785-4303; Fax: 203-785-4301; E-mail: ira.mellman{at}yale.edu
During maturation, dendritic cells (DCs) regulate their capacity to process and present major histocompatibility complex (MHC) IIrestricted 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 marrowderived 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 peptideMHC 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 cellcell contacts) activated cross presentation on MHC I. In contrast, formation of peptideMHC 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.
Key Words: dendritic cells cross presentation MHC class I MHC class II ovalbumin

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