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

Journal Article · · Scientific Reports
DOI:https://doi.org/10.1038/srep04632· OSTI ID:1624703
 [1];  [1];  [2];  [1];  [3];  [1];  [1];  [1];  [3];  [1];  [1]
  1. Duke Univ., Durham, NC (United States). Dept. of Surgery
  2. Duke Univ., Durham, NC (United States). Biostatistics and Bioinformatics; Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
  3. Duke Univ., Durham, NC (United States). Biostatistics and Bioinformatics
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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 CD81 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.

Research Organization:
Duke Univ., Durham, NC (United States)
Sponsoring Organization:
National Institutes of Health (NIH); National Institute of Allergy and Infectious Diseases (NIAID)
Grant/Contract Number:
AC52-07NA27344
OSTI ID:
1624703
Journal Information:
Scientific Reports, Vol. 4, Issue 1; ISSN 2045-2322
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
English

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Science & technology - other topics
MHC class I
Peptide vaccines
Tuberculosis