title: O-mannosylation of the Mycobacterium tuberculosis adhesin Apa is crucial for T cell antigenicity during infection but is expendable for protection.
abstract: Glycosylation is the most abundant post-translational polypeptide chain modification in nature. Although carbohydrate modification of protein antigens from many microbial pathogens constitutes important components of B cell epitopes, the role in T cell immunity is not completely understood. Here, using ELISPOT and polychromatic flow cytometry, we show that O-mannosylation of the adhesin, Apa, of Mycobacterium tuberculosis (Mtb) is crucial for its T cell antigenicity in humans and mice after infection. However, subunit vaccination with both mannosylated and non-mannosylated Apa induced a comparable magnitude and quality of T cell response and imparted similar levels of protection against Mtb challenge in mice. Both forms equally improved waning BCG vaccine-induced protection in elderly mice after subunit boosting. Thus, O-mannosylation of Apa is required for antigenicity but appears to be dispensable for its immunogenicity and protective efficacy in mice. These results have implications for the development of subunit vaccines using post-translationally modified proteins such as glycoproteins against infectious diseases like tuberculosis.
authors.affiliation: Division of Tuberculosis Elimination, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
authors.forename: Subhadra
authors.initials: S
authors.lastname: Nandakumar
authors.forename: Sunil
authors.initials: S
authors.lastname: Kannanganat
authors.forename: Karen M
authors.initials: KM
authors.lastname: Dobos
authors.forename: Megan
authors.initials: M
authors.lastname: Lucas
authors.forename: John S
authors.initials: JS
authors.lastname: Spencer
authors.forename: Sunan
authors.initials: S
authors.lastname: Fang
authors.forename: Melissa A
authors.initials: MA
authors.lastname: McDonald
authors.forename: Jan
authors.initials: J
authors.lastname: Pohl
authors.forename: Kristin
authors.initials: K
authors.lastname: Birkness
authors.forename: Venkateswarlu
authors.initials: V
authors.lastname: Chamcha
authors.forename: Melissa V
authors.initials: MV
authors.lastname: Ramirez
authors.forename: Bonnie B
authors.initials: BB
authors.lastname: Plikaytis
authors.forename: James E
authors.initials: JE
authors.lastname: Posey
authors.forename: Rama Rao
authors.initials: RR
authors.lastname: Amara
authors.forename: Suraj B
authors.initials: SB
authors.lastname: Sable
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006031:Glycosylation; D006801:Humans; D008297:Male; D008358:Mannose / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009163:Mycobacterium bovis / Q000235:genetics / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000235:genetics / Q000276:immunology*
chemical_list: D018829:Adhesins, Bacterial; D000942:Antigens, Bacterial; D032581:Tuberculosis Vaccines; D008358:Mannose