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Impact of MHC class I alleles on the M. tuberculosis antigen-specific CD8+ T-cell response in patients with pulmonary tuberculosis

Genes & Immunity volume 8, pages 334–343 (2007)Cite this article

Abstract

Challenged by scattered understanding of protective immunity to Mycobacterium tuberculosis (MTB), we have mapped peptide epitopes to human leukocyte antigen (HLA)-A*0101, A*0201, A*1101, A*2402, B*0702, B*0801 and B*1501 of the secreted mycobacterial antigen Ag85B, a vaccine candidate that may be associated with immune protection. Affinity (ED50) and half-life (t1/2, off-rate) analysis for individual peptide species on HLA-A and HLA-B molecules revealed binding ranges between 10−3 and 10−7 M. After selection of the best matches, major histocompatibility complex class I/peptide tetramer complexes were constructed to measure the CD8+ T-cell responses directly ex vivo in peripheral blood mononuclear cells (PBMC) derived from 57 patients with acute pulmonary tuberculosis. Three patterns of (allele-) specific CD8+ recognition were identified: (a). Focus on one dominant epitope with additional recognition of several subdominant T-cell epitopes (HLA-A*0301, A*2402, B*0801 and B*1501); (b). Co-dominant recognition of two distinct groups of peptides presented by HLA-B*0702; and (c). Diverse and broad recognition of peptides presented by HLA-A*0201. Peptides that bound with slow off-rates to class I alleles, that is HLA-A*0201, were associated with low frequency of CD8+ T cells in PBMCs from patients with tuberculosis. HLA-B alleles showed fast off-rates in peptide binding and restricted high numbers (up to 6%) of antigen-specific CD8+ T cells in patients with pulmonary tuberculosis.

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Authors and Affiliations

  1. Aeras Global TB Vaccine Foundation, Bethesda, MD, USA

    F F Weichold, S Mueller, D M Hone & J C Sadoff

  2. Department of Pneumology, Hildegardis Hospital, Mainz, Germany

    C Kortsik

  3. Blood Transfusion Center, University of Mainz, Mainz, Germany

    W E Hitzler

  4. THYMED GmbH, Wendelsheim, Germany

    M J Wulf

  5. Department of Microbiology and Tumor Cell Biology Center, Karolinska Institutet, Stockholm, Sweden

    M J Maeurer

Authors
  1. F F Weichold
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  2. S Mueller
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  3. C Kortsik
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  4. W E Hitzler
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  5. M J Wulf
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  6. D M Hone
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  7. J C Sadoff
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Correspondence to M J Maeurer.

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Supplementary Information accompanies the paper on Genes and Immunity website (http://www.nature.com/gene)

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Weichold, F., Mueller, S., Kortsik, C. et al. Impact of MHC class I alleles on the M. tuberculosis antigen-specific CD8+ T-cell response in patients with pulmonary tuberculosis. Genes Immun 8, 334–343 (2007). https://doi.org/10.1038/sj.gene.6364392

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  • DOI: https://doi.org/10.1038/sj.gene.6364392

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