Dataset Information

A Chlamydia trachomatis Strain Expressing Ovalbumin Stimulates an Antigen-Specific CD4⁺ T Cell Response in Mice.

ABSTRACT: Antigen-specific CD4⁺ T cells against Chlamydia are crucial for driving bacterial clearance and mediating protection against reinfection. Although the Chlamydia trachomatis protein Cta1 has been identified to be a dominant murine CD4⁺ T cell antigen, its level of expression during the bacterial developmental cycle and precise localization within the host cell are unknown. Newly developed tools for Chlamydia genetic manipulation have allowed us to generate a C. trachomatis strain expressing a heterologous CD4⁺ T cell epitope from ovalbumin (OVA) consisting of OVA residues 323 to 339 (OVA_323-339). By tagging proteins expressed in C. trachomatis with OVA_323-339, we can begin to understand how protein expression, developmental regulation, and subcellular compartmentalization affect the potential of those proteins to serve as antigens. When OVA_323-339 was expressed as a fusion with green fluorescent protein, we found that we were able to elicit an OT-II T cell response in an antigen-dependent manner, but surprisingly, these T cells were unable to reduce bacterial burden in mice. These data suggest that the subcellular localization of antigen, the level of antigen expression, or the timing of expression within the developmental cycle of Chlamydia may play a crucial role in eliciting a protective CD4⁺ T cell response.

SUBMITTER: Helble JD

PROVIDER: S-EPMC6589065 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Publications

A Chlamydia trachomatis Strain Expressing Ovalbumin Stimulates an Antigen-Specific CD4+ T Cell Response in Mice.

Helble Jennifer D JD Starnbach Michael N MN

Infection and immunity 20190620 7

Antigen-specific CD4+ T cells against Chlamydia are crucial for driving bacterial clearance and mediating protection against reinfection. Although the Chlamydia trachomatis protein Cta1 has been identified to be a dominant murine CD4+ T cell antigen, its level of expression during the bacterial developmental cycle and precise localization within the host cell are unknown. Newly developed tools for Chlamydia genetic manipulation have allowed us to genera ...[more]

PMID: 30988057

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Project description:Allergy is a major public health concern, the main treatment for which is symptomatic relief with anti-inflammatory drugs. A key clinical challenge is to induce specific tolerance in order to control allergen-specific memory B and T cells, and specifically block effector cell responses. Our lab recently developed antigen-specific regulatory T-cell (Treg) therapies as a treatment for adverse responses. Recently, we created a chimeric antigen receptor (CAR) approach in which we engineered a target protein antigen, ovalbumin (OVA), linked with the transmembrane and signal transduction domains, CD28-CD3? to directly target B cells and sensitized mast cells in an allergy model. We named this receptor "BAR" for B-cell Antibody Receptor. Murine or human Tregs, transduced with a BAR containing OVA or control Tregs expressing an unrelated antigen, were successfully expanded in vitro and tested in the murine OVA-alum allergy model with measurable titers of anti-OVA IgE. Because BAR Tregs express the target antigen and could interact with specific IgE on sensitized mast cells, we first demonstrated that intravenously injected OVA-BAR Tregs did not directly lead to a drop in temperature or release of mediators in plasma indicative of anaphylaxis. Forty-eight hours later, mice were challenged intraperitoneally with 200??g OVA to induce an anaphylactic reaction, and temperature immediately measured for 30?min. We found that OVA-BAR Tregs protected mice from hypothermia, whereas mice given control BARs (expressing an unrelated antigen) or PBS showed substantial temperature drops indicative of anaphylaxis when systemically challenged with OVA. Importantly, this effect was also demonstrated in a passive anaphylaxis model in which mice that received anti-OVA IgE antibody were protected from hypothermia when treated with OVA-BAR Tregs prior to systemic OVA challenge. These results provide proof of principle that engineered allergen-specific T-regulatory cells can provide clinical protection against severe allergic reactions in individuals already IgE-sensitized to an allergen.

Dataset Information

A Chlamydia trachomatis Strain Expressing Ovalbumin Stimulates an Antigen-Specific CD4⁺ T Cell Response in Mice.

Publications

A Chlamydia trachomatis Strain Expressing Ovalbumin Stimulates an Antigen-Specific CD4<sup>+</sup> T Cell Response in Mice.

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