Epitopes described in "Expression cloning of an immunodominant family of Mycobacterium tuberculosis antigens using human CD4(+) T cells."

Article Authors:M R Alderson; T Bement; C H Day; L Zhu; D Molesh; Y A Skeiky; R Coler; D M Lewinsohn; S G Reed; D C Dillon
Article Title:Expression cloning of an immunodominant family of Mycobacterium tuberculosis antigens using human CD4(+) T cells.
Reference Detail
Reference ID:942
Abstract:Development of a subunit vaccine for Mycobacterium tuberculosis (Mtb) is likely to be dependent on the identification of T cell antigens that induce strong proliferation and interferon gamma production from healthy purified protein derivative (PPD)(+) donors. We have developed a sensitive and rapid technique for screening an Mtb genomic library expressed in Escherichia coli using Mtb-specific CD4(+) T cells. Using this technique, we identified a family of highly related Mtb antigens. The gene of one family member encodes a 9.9-kD antigen, termed Mtb9.9A. Recombinant Mtb9.9A protein, expressed and purified from E. coli, elicited strong T cell proliferation and IFN-gamma production by peripheral blood mononuclear cells from PPD(+) but not PPD(-) individuals. Southern blot analysis and examination of the Mtb genome sequence revealed a family of highly related genes. A T cell line from a PPD(+) donor that failed to react with recombinant Mtb9.9A recognized one of the other family members, Mtb9.9C. Synthetic peptides were used to map the T cell epitope recognized by this line, and revealed a single amino acid substitution in this region when compared with Mtb9.9A. The direct identification of antigens using T cells from immune donors will undoubtedly be critical for the development of vaccines to several intracellular pathogens.
Affiliations:Department of Immunology, Corixa Corporation, Seattle, Washington 98104, USA. alderson@corixa.com.
Reference Type:Literature
PubMed ID:10662800
Journal:J Exp Med
Journal Volume:191
Article Pages:551-60
Journal ISSN:0022-1007
Article Chemical List:Antigens, Bacterial;Bacterial Vaccines
Article MeSH List:Amino Acid Sequence; Antigens, Bacterial(chemistry; genetics; immunology); Bacterial Vaccines; CD4-Positive T-Lymphocytes(immunology; metabolism; microbiology); Cell Line; Cloning, Molecular; Escherichia coli(genetics; metabolism); Genes, Bacterial; Genomic Library; Humans; Molecular Sequence Data; Mycobacterium tuberculosis(immunology)
Curation Last Updated:2015-06-05 00:13:53