# Interplay of the T Cell Repertoire Development and Early Life Exposure on Incident Risk of Peanut Allergy

> **NIH NIH R21** · JOHNS HOPKINS UNIVERSITY · 2024 · $204,688

## Abstract

ABSTRACT
Peanut allergy (PA) has emerged as a major clinical and public health problem worldwide, due to the dramatic
increase in prevalence, its life-long persistence in most cases, and its associated life-threatening anaphylactic
response. The causes and precise molecular mechanisms underlying the development of PA remain largely
unknown. Available data underscore the early life period (i.e., in-utero and first few years of life) as the critical
window in the development of PA, which is also the critical developmental window for the adaptive immune
system. There is increasing evidence that T cells play a critical role in modulating tolerance to peanut and risk
of PA. Specifically, CD4+ T cells recognize peanut antigens through the engagement of T cell receptors
(TCRs). Each individual has a large and highly variable TCR repertoire which is a major determinant in the
immune response to a given antigen. To date, few studies have longitudinally characterized TCR repertoire
development and dynamics in relation to PA, especially in the context of early life risk or protective factors of
PA such as nutrition and metabolomic alteration and their joint associations with PA development during
childhood. This proposal, motivated by our intriguing previous work and promising preliminary data, will
harness the cutting-edge Adaptive immunoSEQ® technology to deep sequence the TCR ß-chain (TCRß)
complementarity determining region 3 (CDR3) at birth (reflecting in-utero development) and at age 1-2 years
(reflecting postnatal development) in 300 children (150 peanut allergic and 150 non-allergic, non-sensitized
children) from the prospective Boston Birth Cohort (BBC), a NIH-funded U.S. urban, low-resourced
underrepresented multi-ethnic cohort. By leveraging the BBC’s existing biospecimen, genome-wide genotype
data, metabolome, and extensive epidemiological and clinical databases, we aim to investigate: (1)
Longitudinal associations of early life TCRß repertoire development with child risk of PA. We
hypothesize that TCRß repertoire features (i.e., composition, diversity, and dynamics) at birth, at age 1-2
years, and their longitudinal changes are associated with childhood risk of PA. We will further identify peanut-
specific CD4+ T cell subsets with enriched peanut-specific CDR3 (ps-CDR3) sequences or motifs; (2) The
interplay of early life factors, metabolome, and TCRß repertoire on child risk of PA. We hypothesize that
early life nutritional and metabolic factors may influence TCRß repertoire development, and, in turn, may
jointly affect child risk of PA. This proposal is strengthened by its prospective birth cohort design; a strong
multi-disciplinary collaborative team, novel integration of TCRß repertoires with early life exposure to nutrition
and metabolome; and focus on underrepresented, under-studied, high risk, predominantly minority children.
Successful completion of this project will identify novel biomarkers for early risk assessment of PA and new
targ...

## Key facts

- **NIH application ID:** 10898845
- **Project number:** 5R21AI171059-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Xiumei Hong
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $204,688
- **Award type:** 5
- **Project period:** 2023-08-03 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10898845

## Citation

> US National Institutes of Health, RePORTER application 10898845, Interplay of the T Cell Repertoire Development and Early Life Exposure on Incident Risk of Peanut Allergy (5R21AI171059-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10898845. Licensed CC0.

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