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- Title
Mycobacterium tuberculosis Peptides Presented by HLA-E Molecules Are Targets for Human CD8+ T-Cells with Cytotoxic as well as Regulatory Activity.
- Authors
Joosten, Simone A.; van Meijgaarden, Krista E.; van Weeren, Pascale C.; Kazi, Fatima; Geluk, Annemieke; Savage, Nigel D. L.; Drijfhout, Jan W.; Flower, Darren R.; Hanekom, Willem A.; Klein, Michèl R.; Tom H. M. Ottenhoff
- Abstract
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-β. 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.
- Subjects
MYCOBACTERIUM tuberculosis; PEPTIDE synthesis; MOLECULAR genetics; CELL-mediated cytotoxicity; GENETIC regulation; CELL proliferation; GENETICS
- Publication
PLoS Pathogens, 2010, Vol 6, Issue 2, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1000782