Early life imprints the hierarchy of T cell clone sizes

21 Jul 2020  ·  Mario U. Gaimann, Maximilian Nguyen, Jonathan Desponds, Andreas Mayer ·

The adaptive immune system responds to pathogens by selecting clones of cells with specific receptors. While clonal selection in response to particular antigens has been studied in detail, it is unknown how a lifetime of exposures to many antigens collectively shape the immune repertoire. Here, through mathematical modeling and statistical analyses of T cell receptor sequencing data we demonstrate that clonal expansions during a perinatal time window leave a long-lasting imprint on the human T cell repertoire. We demonstrate how the empirical scaling law relating the rank of the largest clones to their size can emerge from clonal growth during repertoire formation. We statistically identify early founded clones and find that they are indeed highly enriched among the largest clones. This enrichment persists even after decades of human aging, in a way that is quantitatively predicted by a model of fluctuating clonal selection. Our work presents a quantitative theory of human T cell dynamics compatible with the statistical laws of repertoire organization and provides a mechanism for how early clonal dynamics imprint the hierarchy of T cell clone sizes with implications for pathogen defense and autoimmunity.

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