Mycobacterium tuberculosis peptides presented by HLA-E molecules are targets for human CD8 T-cells with cytotoxic as well as regulatory activity

Simone A. Joosten, Krista E. van Meijgaarden, Pascale C. van Weeren, Fatima Kazi, Annemieke Geluk, Nigel D.L. Savage, Jan W. Drijfhout, Darren R Flower, Willem A. Hanekom, Michèl R. Klein, Tom H.M. Ottenhoff

Research output: Contribution to journalArticlepeer-review


Tuberculosis (TB) is an escalating global health problem and improved vaccines against TB are urgently needed. HLA-E restricted responses may be of interest for vaccine development since HLA-E displays very limited polymorphism (only 2 coding variants exist), and is not down-regulated by HIV-infection. The peptides from Mycobacterium tuberculosis (Mtb) potentially presented by HLA-E molecules, however, are unknown. Here we describe human T-cell responses to Mtb-derived peptides containing predicted HLA-E binding motifs and binding-affinity for HLA-E. We observed CD8(+) T-cell proliferation to the majority of the 69 peptides tested in Mtb responsive adults as well as in BCG-vaccinated infants. CD8(+) T-cells were cytotoxic against target-cells transfected with HLA-E only in the presence of specific peptide. These T cells were also able to lyse M. bovis BCG infected, but not control monocytes, suggesting recognition of antigens during mycobacterial infection. In addition, peptide induced CD8(+) T-cells also displayed regulatory activity, since they inhibited T-cell proliferation. This regulatory activity was cell contact-dependent, and at least partly dependent on membrane-bound TGF-beta. Our results significantly increase our understanding of the human immune response to Mtb by identification of CD8(+) T-cell responses to novel HLA-E binding peptides of Mtb, which have cytotoxic as well as immunoregulatory activity.
Original languageEnglish
Article numbere1000782
Pages (from-to)e1000782
JournalPlos Pathogens
Issue number2
Publication statusPublished - Feb 2010

Bibliographical note

© 2010 Joosten et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


  • adult
  • antigen presentation
  • bacterial antigens
  • CD8-positive T-lymphocytes
  • cell separation
  • T-lymphocyte epitopes,
  • flow cytometry
  • HLA antigens
  • histocompatibility antigens class I
  • humans
  • infant
  • Lymphocyte activation
  • mycobacterium tuberculosis
  • T-lymphocyte subsets
  • cytotoxic T-lymphocytes
  • regulatory T-lymphocytes
  • tuberculosis
  • tuberculosis vaccines


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