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

<p><strong><span>Background: </span></strong><span>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.</span></p> <p><strong><span>Methods:</span></strong><span> We conducted TCR<span>&beta;</span> 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 TCR<span>&beta;</span> 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 TCR&beta; repertoire.</span></p> <p><strong><span>Results: </span></strong><span>Our study revealed an age-related decline in TCR&beta; 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 TCR&beta;, 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 TCR&beta; repertoire diversity along with age. Furthermore, our predictive models highlight specific TCR&beta; features as potential biomarkers for biological age, supported by their significant correlation.</span></p> <p><strong><span>Conclusion: </span></strong><span>This study provides essential insights into age-related variations in the TCR&beta; repertoire among children, enriching our understanding of pediatric immune system evolution and informing potential disease prevention strategies.</span></p>