Poster Presentation Asia-Pacific Vaccine and Immunotherapy Congress 2024

Age-related dynamics and spectral characteristics of the TCRβ repertoire in healthy children: implications for immune aging (#168)

Mingyan Fang 1 , Stephanie Sun 2
  1. BGI Research, BGI Shenzhen, Shenzhen, Guangdong, China
  2. BGI Australia, Brisbane, QLD, Australia

Background: The T cell receptor (TCR) is crucial for adaptive immunity, providing a diverse repertoire for antigen response. However, despite its clinical importance, baseline characterization of the TCR in the pediatric population remains limited. Methods: We conducted TCRβ sequencing on 325 healthy Chinese children aged 0-18 years, categorized into six age groups, to understand dynamic changes and establish a reference database of TCRβ rearrangements for this demographic. Furthermore, we used cell sorting on 81 samples with flow cytometry to analyze cellular composition and associations, focusing specifically on age-related variations in the TCRβ repertoire. Results: Our study revealed an age-related decline in TCRβ repertoire diversity, marked by increased high-frequency and in-frame clonotypes. This shift in diversity is likely due to age-related variations in CDR3 length and V(D)J gene usage. The analysis of dynamic clonal changes in TCRβ, especially in public clones, suggests a link to perinatal influences and the immune system's evolving personalization. Early-life vaccinations and antigen exposures play a pivotal role in shaping this immune evolution. Notably, a significant association was found between the decrease of CD4+ T naive cells and the diminishing TCRβ repertoire diversity along with age. Furthermore, our predictive models highlight specific TCRβ features as potential biomarkers for biological age, supported by their significant correlation. Conclusion: This study provides essential insights into age-related variations in the TCRβ repertoire among children, enriching our understanding of pediatric immune system evolution and informing potential disease prevention strategies.