Efficient scavenger receptor-mediated uptake and cross-presentation of negatively charged soluble antigens by dendritic cells.
Exogenous antigens endocytosed in large amounts by antigen-presenting cells (APC) are presented on major histocompatibility complex (MHC) class I molecules as well as on class II molecules, a process called cross-presentation. Among APC, dendritic cells (DC) play a key role in cross-presentation by transporting internalized antigen to the cytosol. The present study shows that ovalbumin (OVA) introduced with negative charges by succinylation (Suc-OVA), maleylation (Mal-OVA) or cis-aconitylation (Aco-OVA) was efficiently taken up by DC via scavenger receptors (SR). Mal-OVA and Aco-OVA were efficiently cross-presented by DC, while cross-presentation of Suc-OVA was hardly observed. MHC class I presentation of acylated OVA introduced directly into the cytosol was inefficient and presentation of exogenous native OVA but not of Aco-OVA was markedly augmented by chloroquine, an inhibitor of endosomal acidification, suggesting that deacylation in endosomes or lysosomes is necessary for cross-presentation of acylated OVA. MHC class I presentation of exogenous native OVA and Aco-OVA by DC was blocked by lactacystin and brefeldin A, demonstrating that exogenous antigens taken up by DC are cross-presented through the conventional cytosolic pathway. Therefore, SR-mediated delivery of antigen to DC leads to efficient cross-presentation, although the pathway of chemical modification should be considered.
Shakushiro
Kohsuke
K
Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
Yamasaki
Yasuomi
Y
Nishikawa
Makiya
M
Takakura
Yoshinobu
Y
D000215:Acylation; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D004705:Endocytosis / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006868:Hydrolysis; D051379:Mice; D010047:Ovalbumin / Q000737:chemistry / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology*; D051116:Receptors, Scavenger; D012995:Solubility
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D010047:Ovalbumin