Differential lysosomal proteolysis in antigen-presenting cells determines antigen fate

L Delamarre, M Pack, H Chang, I Mellman… - Science, 2005 - science.org
L Delamarre, M Pack, H Chang, I Mellman, ES Trombetta
Science, 2005science.org
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 …
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.
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