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Antigen-presenting cells (APCs) internalize antigens and presentantigen-derived peptides to T cells. Although APCs have beenthought to exhibit a well-developed capacity for lysosomal proteolysis,here we found that they can exhibit two distinct strategiesupon antigen encounter. Whereas macrophages contained high levelsof lysosomal proteases and rapidly degraded internalized proteins,dendritic cells (DCs) and B lymphocytes were protease-poor,resulting in a limited capacity for lysosomal degradation. Consistentwith these findings, DCs in vivo degraded internalized antigensslowly and thus retained antigen in lymphoid organs for extendedperiods. Limited lysosomal proteolysis also favored antigenpresentation. These results help explain why DCs are able toefficiently accumulate, process, and disseminate antigens andmicrobes systemically for purposes of tolerance and immunity.
Department of Cell Biology and Department of Immunobiology, Ludwig Institute for Cancer Research, Yale University School of Medicine, 333 Cedar Street, Post Office Box 208002, New Haven, CT 06520–8002, USA.
* To whom correspondence should be addressed. E-mail: sergio.trombetta{at}yale.edu (E.S.T); ira.mellman{at}yale.edu (I.M.)
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