Age-Related Dynamics and Spectral Characteristics of the TCRβ Repertoire in Healthy Children: Implications for Immune Aging

Abstract

T-cell receptor (TCR) diversity is crucial for adaptive immunity, yet baseline characterizations in pediatric populations remain sparse. We sequenced the TCRβ chain of 325 healthy Chinese children aged 0–18, categorized into six age groups. We also analyzed cellular composition and TCRβ associations using flow cytometry in 81 of these samples. Our results indicate a decrease in TCRβ diversity with age, characterized by an increase in high-frequency clonotypes and notable changes in CDR3 length and V(D)J gene usage. These changes are influenced by early life vaccinations and antigen exposures. Additionally, we found a significant association between reduced TCRβ diversity and a decrease in CD4⁺ T naïve cells. We also developed a predictive model that identifies specific TCRβ features as potential biomarkers for biological age, validated by their significant correlation with changes in the immune repertoire. These findings enhance our understanding of age-related variations in the TCRβ repertoire among children, providing resourceful information for research on pediatric TCR in health and disease.