About this item:

182 Views | 301 Downloads

Author Notes:

Correspondence: E-mail: SSable@cdc.gov

Subhadra Nandakumar, Sunil Kannanganat, and Suraj B. Sable contributed equally to this work.

Conceived and designed the experiments: SBS SN SK KMD RRA.

Performed the experiments: SN SBS SK KB MVR JEP JSS KMD.

Analyzed the data: SK SN SBS KMD VC.

Contributed reagents/materials/analysis tools: KMD ML JSS SF MAM JP BBP RRA.

Wrote the paper: SBS KMD JP JEP.

The authors thank M. Iademarco and T.M. Shinnick for helpful discussions, S. Malik, M. Willby, and A. Zaunbrecher (Division of Tuberculosis Elimination, CDC) for assistance with CFU enumeration experiments, Mary Leonhardt and Harrison Huntoon (Colorado State University, Fort Collins, CO) for IL-2 assays using 4C3 clone and nApa trypsin digestion, and Amy Yang, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, for providing preclinical BCG vaccine and Mtb Erdman challenge standards.

The findings and conclusions in this publication are those of the authors and do not necessarily represent the official position of CDC, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.

The authors have declared that no competing interests exist.

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Subjects:

Research Funding:

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.

SN and MVR acknowledge the postdoctoral financial assistance from ORISE and Emerging Infectious Diseases fellowship, respectively.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Microbiology
  • Parasitology
  • Virology
  • MICROBIOLOGY
  • PARASITOLOGY
  • VIROLOGY
  • FIBRONECTIN ATTACHMENT PROTEIN
  • DENDRITIC CELLS
  • MANNOSE RECEPTOR
  • 45-KILODALTON GLYCOPROTEIN
  • IMMUNE-RESPONSES
  • PRESENTING CELLS
  • TRANSGENIC MICE
  • VACCINE DESIGN
  • B-CELL
  • GLYCOSYLATION
  • Cytokines
  • T cells
  • Mycobacterium tuberculosis
  • Vaccination and immunization
  • Antigens
  • Spleen
  • Cytotoxic T cells
  • Enzyme-linked immunoassays

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

Show all authors Show less authors

Journal Title:

PLoS Pathogens

Volume:

Volume 9, Number 10

Publisher:

, Pages e1003705-e1003705

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

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.

This is an Open Access work distributed under the terms of the Creative Commons Universal : Public Domain Dedication License (http://creativecommons.org/publicdomain/zero/1.0/).

Creative Commons License

Export to EndNote