A fundamental relationship between TCR diversity, repertoire size and systemic clonal expansion: insights from 30,000 TCR<i>β</i> repertoires.

ABSTRACT:

Introduction

T cell receptor (TCR) diversity is essential for immune defense, yet the mechanisms underlying its decline with age and its variation among individuals remain poorly understood. These patterns are typically attributed to passive processes such as thymic atrophy and cumulative immune exposures. However, this view does not account for the systematic and highly structured variation in TCR diversity observed across large populations.

Methods

We analyze TCRβ repertoires from approximately 30,000 adults using high throughput sequencing. We quantify repertoire size and the contribution of the most expanded clones and evaluate their ability to predict TCRβ diversity across age, sex and Cytomegalovirus exposure using machine learning and linear modeling approaches.

Re

SUBMITTER: Zahid HJ 

PROVIDER: S-EPMC12823994 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature