This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Aoshi, T.
Right arrow Articles by Koide, Y.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Aoshi, T.
Right arrow Articles by Koide, Y.

 Previous Article  |  Next Article 

Infection and Immunity, April 2008, p. 1565-1571, Vol. 76, No. 4
0019-9567/08/$08.00+0     doi:10.1128/IAI.01381-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Identification of an HLA-A*0201-Restricted T-Cell Epitope on the MPT51 Protein, a Major Secreted Protein Derived from Mycobacterium tuberculosis, by MPT51 Overlapping Peptide Screening{triangledown}

Taiki Aoshi,1 Toshi Nagata,2* Mina Suzuki,1 Masato Uchijima,1 Dai Hashimoto,3 Alireza Rafiei,1 Takafumi Suda,3 Kingo Chida,3 and Yukio Koide1

Department of Infectious Diseases,1 Department of Health Science,2 Department of Internal Medicine, Second Division, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan3

Received 15 October 2007/ Returned for modification 26 November 2007/ Accepted 28 December 2007

CD8+ T cells play a pivotal role in protection against Mycobacterium tuberculosis infection. We identified a novel HLA-A*0201-restricted CD8+ T-cell epitope on a dominant secreted antigen of M. tuberculosis, MPT51, in HLA-A*0201 transgenic HHD mice. HHD mice were immunized with plasmid DNA encoding MPT51 with gene gun bombardment, and gamma interferon (IFN-{gamma}) production by the immune splenocytes was analyzed. In response to overlapping synthetic peptides covering the mature MPT51 sequence, the splenocytes were stimulated to produce IFN-{gamma} by only one peptide, p51-70. Three-color flow cytometric analysis of intracellular IFN-{gamma} and cell surface CD4 and CD8 staining revealed that the MPT51 p51-70 peptide contains an immunodominant CD8+ T-cell epitope. Further analysis using computer algorithms permitted identification of a bona fide T-cell epitope, p53-62. A major histocompatibility complex class I stabilization assay using T2 cells confirmed that this epitope binds to HLA-A*0201. The T cells were capable of lysing MPT51 p53-62 peptide-pulsed T2 cells. In addition, MPT51 p53-62-specific memory CD8+ T cells were found in tuberculin skin test-positive HLA-A*0201+ healthy individuals. Use of this HLA-A*0201-restricted CD8+ T-cell epitope for analysis of the role of MPT51-specific T cells in M. tuberculosis infection and for design of vaccines against tuberculosis is feasible.

* Corresponding author. Mailing address: Department of Health Science, Hamamatsu University School of Medicine, 1-20-1 Handa-yama, Higashi-ku, Hamamatsu 431-3192, Japan. Phone and fax: 81-53-435-2332. E-mail: tnagata{at}hama-med.ac.jp

{triangledown} Published ahead of print on 22 January 2008.

Editor: R. P. Morrison

Infection and Immunity, April 2008, p. 1565-1571, Vol. 76, No. 4
0019-9567/08/$08.00+0     doi:10.1128/IAI.01381-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»