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To better understand the mechanisms of intracellular trafficking and presentation of exogenous peptides by antigen-presenting cells (APC), we compared the handling of overlapping 24-mer peptides from HIV Nef either mixed or covalently linked in tandem in one protein. Once internalized, peptides trafficked not only to endosomes but also to cytosol, and activated CD8(+) and CD4(+) T cells. In contrast, whole protein was found to traffic only to the endosomal compartments, and primarily activated CD4(+) T cells. Finally, with adjuvant, overlapping peptides were capable of protecting against lethal viral challenge, whereas the intact protein was less protective. These data suggest that overlapping long peptides are cross-presented through more varied intracellular routes and are more efficient in priming protective immunity than the whole protein.

Original publication

DOI

10.1074/jbc.M809456200

Type

Journal article

Journal

J Biol Chem

Publication Date

03/04/2009

Volume

284

Pages

9184 - 9191

Keywords

Amino Acid Sequence, Animals, Antigen Presentation, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cells, Cultured, Cross-Priming, Dendritic Cells, Mass Spectrometry, Mice, Molecular Sequence Data, Peptides, Phenotype, Protein Transport, Recombinant Proteins