? Project 1 Peanut allergy is a common food allergy that is associated with fatal anaphylactic reaction. While allergy is an IgE mediated disease, accumulating evidence suggests that allergen specific CD4+ T cells play a significant role in disease development. The objective of this project is to establish peanut allergy as a heterogeneous disease with peanut epitope specific T cells as a biomarker to define disease heterogeneity.
The specific aims of this project will include: 1) Identifying peanut specific CD4+ T cell epitope; 2) Examining the phenotype of peanut epitope specific T helper cells; 3) Testing the hypothesis that the phenotype of peanut specific T cells depends on the epitope they recognized; 4) Evaluating phenotype heterogeneity of peanut specific T helper cells in peanut allergic subjects; 5) Testing the hypothesis that phenotype of peanut specific T cells can be used to segregate peanut allergic subjects into 2 distinct subtypes; 5) Establishing a link between phenotype and molecular signature of peanut specific T cells and allergic disease status; 6) Examining the epitope specificity peanut specific regulatory T cells and 7) Testing the hypothesis that regulatory T cells in allergic subjects are functionally impaired. We will use class II tetramers in tracking peanut specific cell and cutting edge technologies, including CyTOF and single cell RNA-seq, in examining peanut specific T cells. A CD154/CD137 assay will also be developed to monitor both peanut specific T effectors and regulatory T cells. The cumulative results will lead to a much better understanding of peanut specific T cells in the pathogenesis of peanut allergy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI135817-04
Application #
10089404
Study Section
Special Emphasis Panel (ZAI1)
Project Start
2018-01-01
Project End
2022-12-31
Budget Start
2021-01-01
Budget End
2021-12-31
Support Year
4
Fiscal Year
2021
Total Cost
Indirect Cost
Name
Benaroya Research Institute at Virginia Mason
Department
Type
DUNS #
076647908
City
Seattle
State
WA
Country
United States
Zip Code
98101
Renand, Amedee; Farrington, Marry; Whalen, Elizabeth et al. (2018) Heterogeneity of Ara h Component-Specific CD4 T Cell Responses in Peanut-Allergic Subjects. Front Immunol 9:1408