1. Identification by mass spectrometry of CD8(+)-T-cell Mycobacterium tuberculosis epitopes within the Rv0341 gene product
- Author
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Karen E. Root, Jarrod A. Marto, David C. Flyer, Jeffrey Shabanowitz, Forest M. White, Helen E. Myers, Venkatesh Ramakrishna, Victor H. Engelhard, Caroline Flournoy, Cara L. Miller, Donald F. Hunt, David H. Canaday, Mark M. Ross, and Melanie McDaniel
- Subjects
Tuberculosis ,Immunology ,Epitopes, T-Lymphocyte ,Biology ,Microbiology ,Epitope ,Gas Chromatography-Mass Spectrometry ,Gene product ,Mycobacterium tuberculosis ,Antigen ,HLA-A2 Antigen ,medicine ,Cytotoxic T cell ,Humans ,Antigens, Bacterial ,Host Response and Inflammation ,Molecular mass ,U937 Cells ,medicine.disease ,biology.organism_classification ,Virology ,Infectious Diseases ,Epitope mapping ,Parasitology ,Peptides ,Epitope Mapping ,T-Lymphocytes, Cytotoxic - Abstract
Identification ofMycobacterium tuberculosisproteins that can provide immunological protection against tuberculosis is essential for the development of a more effective vaccine. To identify new vaccine targets, we have used immunoaffinity chromatography to isolate class I HLA-A*0201-peptide complexes fromM. tuberculosis-infected cells and sequenced the isolated peptides by mass spectrometry. From this material, we have identified three peptides derived from a singleM. tuberculosisprotein that is encoded by theM. tuberculosisRv0341 gene. Although no known protein encoded by the Rv0341 gene has been described, it is predicted to give rise to a 479-amino-acid protein with a molecular mass of 43.9 kDa. The three peptides identified are all nested and were found to be antigenic, in that they were capable of inducing peptide-specific, CD8+T cells from healthy blood donors in vitro and capable of recognizing and lysingM. tuberculosis-infected dendritic cells. This methodology provides a powerful tool for the identification ofM. tuberculosisproteins that can be evaluated as potential vaccine candidates.
- Published
- 2002