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,
Departments of
*
Pathology and
Surgery and
University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213; and
§
University of Pittsburgh Mass Spectrometry Facility, University of Pittsburgh Center for Biotechnology and Bioengineering, Pittsburgh, PA 15219
Dendritic cells and human B cell lines were compared for ability to
present synthetic peptides corresponding to residues 145–159 and
188–203 of human Ig 
-chains to peptide-specific mouse T cell
hybridomas restricted by HLA-DR4Dw4. B cell lines presented both
peptides, but dendritic cells could only efficiently present the latter
epitope. In this paper, we show that dendritic cells degrade the
145–159 peptide, removing four residues from the amino terminus.
Binding of the peptide to the class II restriction element is not
required for this process. The degradation product is resistant to
further cleavage, accumulates in the culture supernatant, and does not
bind to HLA-DR4Dw4 or stimulate T cell reactivity. Cleavage can be
blocked with bestatin, but not with other protease inhibitors tested,
or by a mAb directed against aminopeptidase N (CD13). Addition of an
acetyl group to the amino terminus of peptide 145–159 also blocks
degradation, and allows dendritic cells to present the peptide to
specific T cells with greatly increased efficiency. These results
demonstrate that CD13 on dendritic cells is able to selectively and
efficiently degrade exogenously provided peptide Ags, in a process that
can be blocked by addition of an acetyl group to the amino terminus of
the peptide. Modification of the amino terminus of peptide epitopes
susceptible to degradation may prove to be useful as a general strategy
for enhancing their immunogenicity.
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