Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

1. Mycobacterium tuberculosis and the liver stage of Plasmodium falciparum are intracellular pathogens which are potentially susceptible to cytotoxic T-lymphocytes, a crucial component of the protective immune response to viral infections. Evidence from animal models points to a protective role for cytotoxic T-lymphocytes against M. tuberculosis and P. falciparum, but cytotoxic T-lymphocytes specific for these pathogens have been difficult to identify in man.2. Using a reverse immunogenetic approach, candidate epitopes from selected antigens of P. falciparum and M. tuberculosis were used to detect peptide-specific cytotoxic T-lymphocyte responses in individuals exposed to these pathogens. Cytotoxic T-lymphocyte activity was detected by the 51Cr release cytotoxicity assay and a sensitive ELISPOT assay for single-cell interferon-gamma release.3. In naturally exposed, partially immune Africans in The Gambia, eight largely conserved cytotoxic T-lymphocyte epitopes in P. falciparum, restricted by several different HLA class I alleles, were identified. Several epitopes were also recognized in Tanzanians and cytotoxic T-lymphocytes recognized endogenously processed antigen.4. In tuberculosis patients with HLA-B52, a CD8+ cytotoxic T-lymphocyte epitope was identified in ESAT-6, a secreted antigen specific for M. tuberculosis complex but absent in BCG. Cytotoxic T-lymphocytes exhibited HLA-B52-restricted peptide-specific interferon-gamma release and lytic activity and recognized endogenously processed antigen.5. These studies demonstrate that CD8+ cytotoxic T-lymphocytes specific for mycobacterial and protozoal antigens are induced during natural infections in humans. The identification of these T-cells endorses current strategies to develop cytotoxic T-lymphocyte-inducing vaccines against P. falciparum and M. tuberculosis and highlights candidate antigens for inclusion in subunit vaccines.

Type

Journal article

Journal

Clin Sci (Lond)

Publication Date

11/1998

Volume

95

Pages

531 - 538

Keywords

Animals, Antigens, Bacterial, Antigens, Protozoan, Cytotoxicity Tests, Immunologic, Enzyme-Linked Immunosorbent Assay, Epitopes, Gambia, Humans, Interferon-gamma, Malaria, Mycobacterium tuberculosis, Plasmodium falciparum, T-Lymphocytes, Cytotoxic, Tanzania, Tuberculosis, Vaccines, Synthetic