title: M. tuberculosis T Cell Epitope Analysis Reveals  Paucity of Antigenic Variation and Identifies Rare  Variable TB Antigens.
abstract: Pathogens that evade adaptive immunity typically exhibit antigenic variation. By contrast, it appears that although the chronic human tuberculosis (TB)-causing pathogen Mycobacterium tuberculosis needs to counter host T cell responses, its T cell epitopes are hyperconserved. Here we present an extensive analysis of the T cell epitopes of M. tuberculosis. We combined population genomics with experimental immunology to determine the number and identity of T cell epitope sequence variants in 216 phylogenetically diverse strains of M. tuberculosis. Antigen conservation is indeed a hallmark of M. tuberculosis. However, our analysis revealed a set of seven variable antigens that were immunogenic in subjects with active TB. These findings suggest that M. tuberculosis uses mechanisms other than antigenic variation to evade T cells. T cell epitopes that exhibit sequence variation may not be subject to the same evasion mechanisms, and hence vaccines that include such variable epitopes may be more efficacious.
authors.forename: Mireia
authors.initials: M
authors.lastname: Coscolla
authors.forename: Richard
authors.initials: R
authors.lastname: Copin
authors.forename: Jayne
authors.initials: J
authors.lastname: Sutherland
authors.forename: Florian
authors.initials: F
authors.lastname: Gehre
authors.forename: Bouke
authors.initials: B
authors.lastname: de Jong
authors.forename: Olumuiya
authors.initials: O
authors.lastname: Owolabi
authors.forename: Georgetta
authors.initials: G
authors.lastname: Mbayo
authors.forename: Federica
authors.initials: F
authors.lastname: Giardina
authors.forename: Joel D
authors.initials: JD
authors.lastname: Ernst
authors.forename: Sebastien
authors.initials: S
authors.lastname: Gagneux
mesh_terms: D000940:Antigenic Variation; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000235:genetics* / Q000276:immunology*; D014644:Genetic Variation; D016680:Genome, Bacterial; D006801:Humans; D057131:Immune Evasion; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000235:genetics* / Q000276:immunology*; D010802:Phylogeny; D014376:Tuberculosis / Q000276:immunology / Q000382:microbiology*
chemical_list: D000942:Antigens, Bacterial; D018984:Epitopes, T-Lymphocyte