Persisting fetal clonotypes influence the structure and overlap of adult human T cell receptor repertoires

TL;DR

This study shows that fetal T-cell clonotypes persist into adulthood, shaping the shared 'public' T-cell receptor repertoire and influencing immune diversity across the lifespan.

Contribution

It reveals that fetal-origin T-cell clones are long-lived and contribute significantly to the adult TCR repertoire, a novel insight into immune system development.

Findings

Fetal T-cell clones persist into adulthood for decades.

Shared public clonotypes originate during pregnancy.

Adult TCR diversity is influenced by long-lived fetal clones.

Abstract

The diversity of T-cell receptors recognizing foreign pathogens is generated through a highly stochastic recombination process, making the independent production of the same sequence rare. Yet unrelated individuals do share receptors, which together constitute a "public" repertoire of abundant clonotypes. The TCR repertoire is initially formed prenatally, when the enzyme inserting random nucleotides is downregulated, producing a limited diversity subset. By statistically analyzing deep sequencing T-cell repertoire data from twins, unrelated individuals of various ages, and cord blood, we show that T-cell clones generated before birth persist and maintain high abundances in adult organisms for decades, slowly decaying with age. Our results suggest that large, low-diversity public clones are created during pregnancy, and survive over long periods, providing the basis of the public repertoire.