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Infectious disease

Methylation makes a difference

Nature Reviews Immunology volume 4, page 658 (2004)Cite this article

HBHA is a cell-surface protein antigen, and the native protein (nHBHA) is post-translationally modified by methylation of lysine-rich repeats in the carboxy-terminal domain; however, recombinant HBHA (rHBHA) produced by Escherichia coli is not methylated. Because T cells that are isolated from healthy humans infected with M. tuberculosis produce large amounts of interferon-γ (IFN-γ) in response to HBHA, whereas T cells from patients with active tuberculosis do not, Temmerman et al. investigated the role of HBHA methylation in the immune response to M. tuberculosis.

Peripheral-blood mononuclear cells (PBMCs) from healthy individuals infected with M. tuberculosis secreted greater levels of IFN-γ in response to nHBHA than in response to rHBHA, and the proportion of individuals with nHBHA-responsive PBMCs was much greater for the healthy infected individuals than for patients with tuberculosis. The importance of methylation was confirmed by the observation that IFN-γ production was enhanced when rHBHA was methylated in vitro and by the finding that splenocytes from mice infected with Mycobacterium bovis bacillus Calmette-Guérin (BCG) produced considerably more IFN-γ in response to nHBHA than in response to rHBHA.

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ORIGINAL RESEARCH PAPER

  1. Temmerman, S. et al. Methylation-dependent T cell immunity to Mycobacterium tuberculosis heparin-binding hemagglutinin. Nature Med. 8 August 2004 (doi:10/1038/nm1090).

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Authors
  1. Karen Honey
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Honey, K. Methylation makes a difference. Nat Rev Immunol 4, 658 (2004). https://doi.org/10.1038/nri1444

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  • DOI: https://doi.org/10.1038/nri1444

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