Epitopes described in "Epitope mapping of the immunodominant antigen TB10.4 and the two homologous proteins TB10.3 and TB12.9, which constitute a subfamily of the esat-6 gene family."

Article Authors:Rikke Louise Vinther Skjøt; Inger Brock; Sandra M Arend; Martin E Munk; Michael Theisen; Tom H M Ottenhoff; Peter Andersen
Article Title:Epitope mapping of the immunodominant antigen TB10.4 and the two homologous proteins TB10.3 and TB12.9, which constitute a subfamily of the esat-6 gene family.
Reference Detail
Reference ID:743
Abstract:The human T-cell recognition of the low-molecular-mass culture filtrate antigen TB10.4 was evaluated in detail. The molecule was strongly recognized by T cells isolated from tuberculosis (TB) patients and from BCG-vaccinated donors. The epitopes on TB10.4 were mapped with overlapping peptides and found to be distributed throughout the molecule. The broadest response was found in TB patients, whereas the response in BCG-vaccinated donors was focused mainly toward a dominant epitope located in the N terminus (amino acids 1 to 18). The gene encoding TB10.4 was found to belong to a subfamily within the esat-6 family that consists of the three highly homologous proteins TB10.4, TB10.3, and TB12.9 (Rv0288, Rv3019c, and Rv3017c, respectively). Southern blot analysis combined with database searches revealed that the three members of the TB10.4 family were present only in strains of the Mycobacterium tuberculosis complex, including BCG, and M. kansasii, whereas other atypical mycobacteria had either one (M. avium, M. intracellulare, and M. marinum) or none (M. scrofulaceum, M. fortuitum, and M. szulgai) of the genes. The fine specificity of the T-cell response to the three closely related esat-6 family members was markedly different, with only a few epitopes shared between the molecules. Minimal differences in the amino acid sequence translated into large differences in recognition by T cells and secretion of gamma interferon. In general, the peptides from TB10.4 stimulated the largest responses, but epitopes unique to both TB10.3 and TB12.9 were found. The relevance of the findings for TB vaccine development and as a potential mechanism for immune evasion is discussed.
Affiliations:Department of TB Immunology, Statens Serum Institute, Copenhagen, Denmark.
Reference Type:Literature
PubMed ID:12228269
Journal:Infect Immun
Journal Volume:70
Article Pages:5446-53
Journal ISSN:0019-9567
Article Chemical List:Antigens, Bacterial;BCG Vaccine;Bacterial Proteins;ESAT-6 protein, Mycobacterium tuberculosis;Immunodominant Epitopes;Interferon-gamma
Article MeSH List:Amino Acid Sequence; Antigens, Bacterial(genetics); BCG Vaccine(pharmacology); Bacterial Proteins; Case-Control Studies; Epitope Mapping; Humans; Immunodominant Epitopes(genetics); In Vitro Techniques; Interferon-gamma(biosynthesis); Lymphocyte Activation; Molecular Sequence Data; Mycobacterium tuberculosis(genetics; immunology); Sequence Homology, Amino Acid; T-Lymphocytes(immunology); Tuberculosis, Pulmonary(immunology; microbiology)
Curation Last Updated:2015-07-30 20:01:46