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

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.