Classically restricted human CD8+ T lymphocytes derived from Mycobacterium tuberculosis-infected cells: Definition of antigenic specificity

David Lewinsohn, L. Zhu, V. J. Madison, D. C. Dillon, S. P. Fling, S. G. Reed, K. H. Grabstein, M. R. Alderson

Research output: Contribution to journalArticle

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Abstract

Previous studies in murine and human models have suggested an important role for HLA Ia-restricted CD8+ T cells in host defense to Mycobacterium tuberculosis (Mtb). Therefore, understanding the Ags presented via HLA-Ia will be important in understanding the host response to Mtb and in rational vaccine design. We have used monocyte-derived dendritic cells in a limiting dilution analysis to generate Mtb-specific CD8+ T cells. Two HLA-Ia-restricted CD8+ T cell clones derived by this method were selected for detailed analysis. One was HLA-B44 restricted, and the other was HLA-B14 restricted. Both were found to react with Mtb-infected, but not bacillus Calmette-Guérin-infected, targets. For both these clones, the Ag was identified as culture filtrate protein 10 (CFP10)/Mtb11, a 10.8-kDa protein not expressed by bacillus Calmette-Guérin. Both clones were inhibited by the anti-class I Ab and anti-HLA-B,C Abs. Using a panel of CFP10/Mtb11-derived 15-aa peptides overlapping by 11 aa, the region containing the epitopes for both clones has been defined. Minimal 10-aa epitopes were defined for both clones. CD8+ effector cells specific for these two epitopes are present at high frequency in the circulating pool. Moreover, the CD8+ T cell response to CFP10/Mtb11 can be largely accounted for by the two epitopes defined herein, suggesting that this is the immunodominant response for this purified protein derivative-positive donor. This study represents the first time CD8+ T cells generated against Mtb-infected APC have been used to elucidate an Mtb-specific CD8+ T cell Ag.

Original languageEnglish (US)
Pages (from-to)439-446
Number of pages8
JournalJournal of Immunology
Volume166
Issue number1
StatePublished - Jan 1 2001
Externally publishedYes

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Mycobacterium tuberculosis
Epitopes
T-Lymphocytes
Clone Cells
Proteins
Bacillus
HLA-B14 Antigen
HLA-B44 Antigen
HLA-C Antigens
HLA-B Antigens
Dendritic Cells
Monocytes
Vaccines
Peptides

ASJC Scopus subject areas

  • Immunology

Cite this

Lewinsohn, D., Zhu, L., Madison, V. J., Dillon, D. C., Fling, S. P., Reed, S. G., ... Alderson, M. R. (2001). Classically restricted human CD8+ T lymphocytes derived from Mycobacterium tuberculosis-infected cells: Definition of antigenic specificity. Journal of Immunology, 166(1), 439-446.

Classically restricted human CD8+ T lymphocytes derived from Mycobacterium tuberculosis-infected cells : Definition of antigenic specificity. / Lewinsohn, David; Zhu, L.; Madison, V. J.; Dillon, D. C.; Fling, S. P.; Reed, S. G.; Grabstein, K. H.; Alderson, M. R.

In: Journal of Immunology, Vol. 166, No. 1, 01.01.2001, p. 439-446.

Research output: Contribution to journalArticle

Lewinsohn, D, Zhu, L, Madison, VJ, Dillon, DC, Fling, SP, Reed, SG, Grabstein, KH & Alderson, MR 2001, 'Classically restricted human CD8+ T lymphocytes derived from Mycobacterium tuberculosis-infected cells: Definition of antigenic specificity', Journal of Immunology, vol. 166, no. 1, pp. 439-446.
Lewinsohn, David ; Zhu, L. ; Madison, V. J. ; Dillon, D. C. ; Fling, S. P. ; Reed, S. G. ; Grabstein, K. H. ; Alderson, M. R. / Classically restricted human CD8+ T lymphocytes derived from Mycobacterium tuberculosis-infected cells : Definition of antigenic specificity. In: Journal of Immunology. 2001 ; Vol. 166, No. 1. pp. 439-446.
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