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Sci Rep. 2014 Apr 23;4:4632. doi: 10.1038/srep04632.

High-throughput identification and dendritic cell-based functional validation of MHC class I-restricted Mycobacterium tuberculosis epitopes.

Author information

1
1] Departments of Surgery, Duke University Medical Center, Durham, NC 27710 [2].
2
1] Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC 27710 [2].
3
Departments of Surgery, Duke University Medical Center, Durham, NC 27710.
4
Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC 27710.

Abstract

Emergence of drug-resistant strains of the pathogen Mycobacterium tuberculosis (Mtb) and the ineffectiveness of BCG in curtailing Mtb infection makes vaccine development for tuberculosis an important objective. Identifying immunogenic CD8+ T cell peptide epitopes is necessary for peptide-based vaccine strategies. We present a three-tiered strategy for identifying and validating immunogenic peptides: first, identify peptides that form stable complexes with class I MHC molecules; second, determine whether cytotoxic T lymphocytes (CTLs) raised against the whole protein antigen recognize and lyse target cells pulsed with peptides that passed step 1; third, determine whether peptides that passed step 2, when administered in vivo as a vaccine in HLA-A2 transgenic mice, elicit CTLs that lyse target cells expressing the whole protein antigen. Our innovative approach uses dendritic cells transfected with Mtb antigen-encoding mRNA to drive antigen expression. Using this strategy, we have identified five novel peptide epitopes from the Mtb proteins Apa, Mtb8.4 and Mtb19.

PMID:
24755960
PMCID:
PMC4894389
DOI:
10.1038/srep04632
[Indexed for MEDLINE]
Free PMC Article
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