Identification and Investigation of CD4+ T cell Clonotypes Comprising a Polyclonal Repertoire Against Aeroallergen in a Murine Model of Allergic Asthma
NIAID - National Institute of Allergy and Infectious Diseases
About This Grant
PROJECT SUMMARY/ABSTRACT Allergic asthma presents as either T2-high (Th2/eosinophilic) or T2-low (Th17/neutrophilic) inflammation. While external factors like co-stimulation and cytokines shape Th cell fate, the role of T cell receptor (TCR) affinity in directing Th2 vs. Th17 differentiation remains unclear. Our lab developed a fungal protease (Alp1)-driven allergic lung inflammation model and essential reagents, including an IL-5/IL-17A reporter mouse. We observed that Alp1 sensitization primarily induces a Th2 response (~30% IL-5+ Th cells, eosinophilia) but also elicits a smaller Th17 response (~5% IL-17A+ Th cells, neutrophilia). This suggests TCR-intrinsic factors influence effector fate. We hypothesize that TCR affinity dictates Th2 vs. Th17 differentiation in response to fungal protease allergens. A major limitation in allergy research is the lack of tools to study allergen-specific Th cells. We aim to develop peptide-MHCII tetramers to examine TCR affinity and its impact on Th2/Th17 fate within oligoclonal populations. Additionally, we will generate a TCR transgenic mouse and engineered protease allergens to directly test TCR affinity’s role in Th cell differentiation. Our lab has identified an immunodominant Alp1 epitope (aa 194-202) and developed a functional peptide- MHCII tetramer. We also created a transgenic mouse expressing tagged-MHCII in dendritic cells, enabling in vivo epitope discovery. With these tools, we will achieve the following aims: Aim 1: Define the relationship between TCR affinity and Th2/Th17 fate in a polyclonal response. Aim 2: Directly test the causal role of TCR affinity in Th2/Th17 differentiation. This study will advance allergy and immunology research by overcoming technical barriers in epitope discovery and immunodominance. Our transgenic models, cytokine reporters, and tetramer technology will provide a framework for understanding allergen-driven Th cell responses, with implications for new diagnostic and therapeutic strategies in allergic diseases.
Grant Summary
Identification and Investigation of CD4+ T cell Clonotypes Comprising a Polyclonal Repertoire Against Aeroallergen in a Murine Model of Allergic Asthma is a NIAID - National Institute of Allergy and Infectious Diseases grant providing up to $421K for university, nonprofit, healthcare org. Applications are due 2028-03-31 (open). Check eligibility and apply with FindGrants.
Focus Areas
Eligibility
How to Apply
Up to $421K
2028-03-31
- 1Confirm your organization is eligible for Identification and Investigation of CD4+ T cell Clonotypes Comprising a Polyclonal Repertoire Against Aeroallergen in a Murine Model of Allergic Asthma from NIAID - National Institute of Allergy and Infectious Diseases, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NIAID - National Institute of Allergy and Infectious Diseases before the deadline.
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Identification and Investigation of CD4+ T cell Clonotypes Comprising a Polyclonal Repertoire Against Aeroallergen in a Murine Model of Allergic Asthma: Frequently Asked Questions
Who is eligible for the Identification and Investigation of CD4+ T cell Clonotypes Comprising a Polyclonal Repertoire Against Aeroallergen in a Murine Model of Allergic Asthma?
Identification and Investigation of CD4+ T cell Clonotypes Comprising a Polyclonal Repertoire Against Aeroallergen in a Murine Model of Allergic Asthma is offered by NIAID - National Institute of Allergy and Infectious Diseases and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Identification and Investigation of CD4+ T cell Clonotypes Comprising a Polyclonal Repertoire Against Aeroallergen in a Murine Model of Allergic Asthma provide?
Identification and Investigation of CD4+ T cell Clonotypes Comprising a Polyclonal Repertoire Against Aeroallergen in a Murine Model of Allergic Asthma provides up to $421K per award from NIAID - National Institute of Allergy and Infectious Diseases. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Identification and Investigation of CD4+ T cell Clonotypes Comprising a Polyclonal Repertoire Against Aeroallergen in a Murine Model of Allergic Asthma deadline?
Applications for Identification and Investigation of CD4+ T cell Clonotypes Comprising a Polyclonal Repertoire Against Aeroallergen in a Murine Model of Allergic Asthma are due 2028-03-31 (open). Because deadlines can change, verify the date with the funder, NIAID - National Institute of Allergy and Infectious Diseases, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Identification and Investigation of CD4+ T cell Clonotypes Comprising a Polyclonal Repertoire Against Aeroallergen in a Murine Model of Allergic Asthma?
To apply for Identification and Investigation of CD4+ T cell Clonotypes Comprising a Polyclonal Repertoire Against Aeroallergen in a Murine Model of Allergic Asthma, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NIAID - National Institute of Allergy and Infectious Diseases.