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Efficient scavenger receptor‐mediated uptake and cross‐presentation of negatively charged soluble antigens by dendritic cells
Author(s) -
Shakushiro Kohsuke,
Yamasaki Yasuomi,
Nishikawa Makiya,
Takakura Yoshinobu
Publication year - 2004
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2004.01871.x
Subject(s) - cross presentation , brefeldin a , antigen presentation , microbiology and biotechnology , mhc class i , ovalbumin , endosome , antigen processing , antigen , scavenger receptor , biology , cytosol , antigen presenting cell , major histocompatibility complex , chemistry , immunology , immune system , biochemistry , t cell , intracellular , endoplasmic reticulum , golgi apparatus , lipoprotein , cholesterol , enzyme
Summary 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.