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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Mycobacterium tuberculosis peptides presented by HLA-E molecules are targets for human CD8+ T-cells with cytotoxic as well as regulatory activity
PLoS Pathogens, Volume 6, No. 2, Article e1000782, Year 2010
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Description
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. © 2010 Joosten et al.
Authors & Co-Authors
Joosten, Simone A.
Netherlands, Leiden
Leids Universitair Medisch Centrum
van Meijgaarden, Krista E.
Netherlands, Leiden
Leids Universitair Medisch Centrum
Van Weeren, Pascale C.
Netherlands, Leiden
Leids Universitair Medisch Centrum
Kazi, Fatima
Netherlands, Leiden
Leids Universitair Medisch Centrum
Geluk, Annemieke
Netherlands, Leiden
Leids Universitair Medisch Centrum
Savage, Nigel D.L.
Netherlands, Leiden
Leids Universitair Medisch Centrum
Drijfhout, Jan Wouter
Netherlands, Leiden
Leids Universitair Medisch Centrum
Flower, Darren R.
United Kingdom, Oxford
University of Oxford
Hanekom, Willem Albert
South Africa, Observatory
South African Tuberculosis Vaccine Initiative
Klein, Michèl R.
Netherlands, Leiden
Leids Universitair Medisch Centrum
Ottenhoff, Tom H.M.
Netherlands, Leiden
Leids Universitair Medisch Centrum
Statistics
Citations: 141
Authors: 11
Affiliations: 3
Identifiers
Doi:
10.1371/journal.ppat.1000782
ISSN:
15537366
e-ISSN:
15537374
Research Areas
Infectious Diseases