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Science 307 (5715): 1630-1634

Copyright © 2005 by the American Association for the Advancement of Science

Differential Lysosomal Proteolysis in Antigen-Presenting Cells Determines Antigen Fate

Lélia Delamarre, Margit Pack, Henry Chang, Ira Mellman,* E. Sergio Trombetta*

Abstract: Antigen-presenting cells (APCs) internalize antigens and present antigen-derived peptides to T cells. Although APCs have been thought to exhibit a well-developed capacity for lysosomal proteolysis, here we found that they can exhibit two distinct strategies upon antigen encounter. Whereas macrophages contained high levels of lysosomal proteases and rapidly degraded internalized proteins, dendritic cells (DCs) and B lymphocytes were protease-poor, resulting in a limited capacity for lysosomal degradation. Consistent with these findings, DCs in vivo degraded internalized antigens slowly and thus retained antigen in lymphoid organs for extended periods. Limited lysosomal proteolysis also favored antigen presentation. These results help explain why DCs are able to efficiently accumulate, process, and disseminate antigens and microbes 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} (E.S.T); ira.mellman{at} (I.M.)

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Antigen Requirements for Efficient Priming of CD8+ T Cells by Leishmania major-Infected Dendritic Cells.
S. Bertholet, A. Debrabant, F. Afrin, E. Caler, S. Mendez, K. S. Tabbara, Y. Belkaid, and D. L. Sacks (2005)
Infect. Immun. 73, 6620-6628
   Abstract »    Full Text »    PDF »
Chloroquine enhances human CD8+ T cell responses against soluble antigens in vivo.
D. Accapezzato, V. Visco, V. Francavilla, C. Molette, T. Donato, M. Paroli, M. U. Mondelli, M. Doria, M. R. Torrisi, and V. Barnaba (2005)
J. Exp. Med. 202, 817-828
   Abstract »    Full Text »    PDF »
Dendritic cells star in Vancouver.
E. Klechevsky, H. Kato, and A.-M. Sponaas (2005)
J. Exp. Med. 202, 5-10
   Abstract »    Full Text »    PDF »
Autophagy promotes MHC class II presentation of peptides from intracellular source proteins.
J. Dengjel, O. Schoor, R. Fischer, M. Reich, M. Kraus, M. Muller, K. Kreymborg, F. Altenberend, J. Brandenburg, H. Kalbacher, et al. (2005)
PNAS 102, 7922-7927
   Abstract »    Full Text »    PDF »
APC proteolysis not overdone.
N. LeBrasseur (2005)
J. Cell Biol. 169, 16
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