HLA-B*35-restricted CD8 T cell epitopes in the antigen 85 complex of Mycobacterium tuberculosis


Klein, MR; Smith, SM; Hammond, AS; Ogg, GS; King, AS; Vekemans, J; Jaye, A; Lukey, PT; McAdam, K; (2001) HLA-B*35-restricted CD8 T cell epitopes in the antigen 85 complex of Mycobacterium tuberculosis. The Journal of infectious diseases, 183 (6). pp. 928-34. ISSN 0022-1899

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Abstract

Few target epitopes have been described for human CD8 T lymphocytes in antigens of Mycobacterium tuberculosis. By use of a reverse immunogenetics approach, 23 motif-bearing peptides of the Ag85 complex were tested for binding to HLA-B*35, one of the common B-types in West Africa. Three 9-mer peptides bound with high affinity to HLA-B*3501 and displayed low dissociation rates of peptide-major histocompatibility complexes (MHCs). IC(50) and half-life values of peptide-MHC class I complexes were in the same range as reported earlier for other immunogenic peptides. Immune responses against peptide Ag85C (aa 204-212) WPTLIGLAM were characterized in detail. Peptide-stimulated effector cells were able to kill macrophages infected with M. tuberculosis or bacille Calmette-Guérin. Peptide-specific CD8 T cells could be visualized by using HLA-B*3501 tetramers and were shown to produce interferon-gamma and tumor necrosis factor-alpha. Together with other published epitopes, these peptides can be used to study more closely the role of CD8 T cells in mycobacterial infection and tuberculosis.

Item Type: Article
Keywords: Class-i molecules, peptide-binding, antimicrobial activity, infection, identification, lymphocytes, mice, vaccination, resistance, protection, Algorithms, Amino Acid Motifs, Antigens, Bacterial, immunology, CD8-Positive T-Lymphocytes, immunology, Cells, Cultured, Cytotoxicity Tests, Immunologic, Epitopes, T-Lymphocyte, immunology, HLA-B35 Antigen, immunology, Human, Interferons, biosynthesis, Macrophages, microbiology, Mycobacterium tuberculosis, immunology, Peptides, immunology, Support, Non-U.S. Gov't
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Clinical Research
PubMed ID: 11237810
Web of Science ID: 167114500013
URI: http://researchonline.lshtm.ac.uk/id/eprint/16428

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