INTRODUCTION: Tuberculosis (TB) remains the first cause of death from infection caused by a bacterial pathogen. Chemotherapy does not eradicate Mycobacterium tuberculosis (Mtb) from human lungs, and the pathogen causes a latent tuberculosis infection that cannot be prevented by the currently available Bacille Calmette Guerin (BCG) vaccine, which is ineffective in the prevention of pulmonary TB in adults. HLA-E-restricted CD8+ T lymphocytes are essential players in protective immune responses against Mtb. Hence, expanding this population in vivo or ex vivo may be crucial for vaccination or immunotherapy against TB. METHODS: The enzymatically inactive Bordetella pertussis adenylate cyclase (CyaA) toxoid is an effective tool for delivering peptide epitopes into the cytosol of antigen-presenting cells (APC) for presentation and stimulation of specific CD8+ T-cell responses. In this study, we have investigated the capacity of the CyaA toxoid to deliver Mtb epitopes known to bind HLA-E for the expansion of human CD8+ T cells in vitro. RESULTS: Our results show that the CyaA-toxoid containing five HLA-E-restricted Mtb epitopes causes significant expansion of HLA-E-restricted antigen-specific CD8+ T cells, which produce IFN-γ and exert significant cytotoxic activity towards peptide-pulsed macrophages. DISCUSSION: HLA-E represents a promising platform for the development of new vaccines; our study indicates that the CyaA construct represents a suitable delivery system of the HLA-E-binding Mtb epitopes for ex vivo and in vitro expansion of HLA-E-restricted CD8+ T cells inducing a predominant Tc1 cytokine profile with a significant increase of IFN-γ production, for prophylactic and immunotherapeutic applications against Mtb.

• Keywords
• Bordetella pertussis adenylate cyclase, HLA-E, Mycobacterium tuberculosis, cytotoxic t lymphocytes, immunotherapy, peptides, vaccine,
• MeSH
• Adenylyl Cyclases MeSH
• HLA-E Antigens MeSH
• Bordetella pertussis MeSH
• CD8-Positive T-Lymphocytes MeSH
• Epitopes MeSH
• Humans MeSH
• Histocompatibility Antigens Class I MeSH
• Mycobacterium tuberculosis * MeSH
• Peptides MeSH
• Toxoids MeSH
• Tuberculosis * prevention & control   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Adenylyl Cyclases MeSH
• HLA-E Antigens MeSH
• Epitopes MeSH
• Histocompatibility Antigens Class I MeSH
• Peptides MeSH
• Toxoids MeSH