O-mannosylation of the Mycobacterium tuberculosis Adhesin Apa Is Crucial for T Cell Antigenicity during Infection but Is Expendable for Protection

• Type of Material: Article
• Authors: Subhadra Nandakumar, Centers for Disease Control and Prevention; Sunil Kannanganat, Emory University; Karen M. Dobos, Colorado State University; Megan Lucas, Colorado State University; John S. Spencer, Colorado State University; Sunan Fang, Centers for Disease Control and Prevention; Melissa A. McDonald, Centers for Disease Control and Prevention; Jan Pohl, Emory University; Kristin Birkness, Centers for Disease Control and Prevention; Venkateswarlu Chamcha, Emory University; Melissa V. Ramirez, Centers for Disease Control and Prevention; Bonnie B. Plikaytis, Centers for Disease Control and Prevention; James E. Posey, Centers for Disease Control and Prevention; Rama Amara, Emory University; Suraj B. Sable, Centers for Disease Control and Prevention
• Language: English
• Date: 2013-10-10
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
• License: Creative Commons Creative Commons CC0 1.0 Universal
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.ppat.1003705
• Title of Journal or Parent Work: PLoS Pathogens
• ISSN: 1553-7366
• Volume: 9
• Issue: 10
• Start Page: e1003705
• End Page: e1003705
• Grant/Funding Information: SN and MVR acknowledge the postdoctoral financial assistance from ORISE and Emerging Infectious Diseases fellowship, respectively.; This work was supported by Georgia Research Alliance (to SBS and RRA as principle investigators and JEP and TM Shinnick as co-investigators), National Institute of Health/National Institute of Allergy and Infectious Diseases contract HHSN266200400091c (to KMD), and Centers for Disease Control and Prevention intramural grants.
• Keywords: VACCINE DESIGN; Science & Technology; PRESENTING CELLS; 45-KILODALTON GLYCOPROTEIN; Life Sciences & Biomedicine; Antigens; MICROBIOLOGY; DENDRITIC CELLS; PARASITOLOGY; Cytokines; T cells; IMMUNE-RESPONSES; Virology; VIROLOGY; GLYCOSYLATION; Cytotoxic T cells; Vaccination and immunization; B-CELL; MANNOSE RECEPTOR; TRANSGENIC MICE; Microbiology; FIBRONECTIN ATTACHMENT PROTEIN; Spleen; Parasitology; Mycobacterium tuberculosis; Enzyme-linked immunoassays
• Research Categories: Biology, Virology; Biology, Microbiology; Health Sciences, Immunology

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.