Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 284, Issue 14, Pages 9184-9191Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M809456200
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Funding
- Mary Kinross Charitable Trust's Fund
- University of Oxford's Proof of Concept Fund
- MRC [MC_U137884177, MC_U137881015] Funding Source: UKRI
- Medical Research Council [MC_U137884177, MC_U137881015] Funding Source: researchfish
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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(+) Tcells. 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.
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