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

Nandakumar, Subhadra; Kannanganat, Sunil; Dobos, Karen M.; Lucas, Megan; Spencer, John S.; Fang, Sunan; McDonald, Melissa A.; Pohl, Jan; Birkness, Kristin; Chamcha, Venkateswarlu; Ramirez, Melissa V.; Plikaytis, Bonnie B.; Posey, James E.; Amara, Rama Rao; Sable, Suraj B.

doi:10.1371/journal.ppat.1003705

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

Published Date:

Oct 10 2013

Publisher's site:

http://dx.doi.org/10.1371/journal.ppat.1003705 New Site Icon

Source:

PLoS Pathog. 2013; 9(10).

[PDF-1.93 MB]

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Alternative Title:

PLoS Pathog

Personal Author:

Nandakumar, Subhadra ; Kannanganat, Sunil ; Dobos, Karen M. ; Lucas, Megan ; Spencer, John S. ; ... More ▼

Description:

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.

Subject:

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Document Type:

Journal Article

Funding:

HHSN266200400091C/PHS HHS/United States ; R01 AI071852/AI/NIAID NIH HHS/United States ; U19 AI074073/AI/NIAID NIH HHS/United States ;

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CDC Public Access

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