HLA-A^∗0201-restricted cytotoxic T-cell epitopes in three PE/PPE family proteins of Mycobacterium tuberculosis

Abstract

CD8⁺ T cells are thought to play an important role in protective immunity against tuberculosis. We report the identification of three peptides derived from Rv1818c, Rv3812 and Rv3018c proteins of Mycobacterium tuberculosis that bound to HLA-A^∗0201 molecules and their ability to induce in vitro T-cell response in peripheral blood lymphocytes from HLA-A^∗0201-positive healthy individuals (PPD+) and patients with TB. The peptide-specific cytotoxic T lymphocytes (CTL) generated were capable of recognizing peptide pulsed targets. Three 9-mer peptides bound with high affinity to HLA-A^∗0201 and displayed low dissociation rates of the bound peptide from HLA. Epitope-specific recognition was demonstrated by the release of perforin and -interferon. Overall, our results demonstrate the presence of HLA class I-restricted CD8⁺ CTL against proteins from PE and PPE proteins of M. tuberculosis and identify epitopes that are strongly recognized by HLA-A^∗0201-restricted CD8⁺ T cells in humans. These epitopes thus represent potential subunit components for the design of vaccines against tuberculosis.