A fundamental relationship between TCR diversity, repertoire size and systemic clonal expansion: insights from 30,000 TCRβ repertoires

We propose that intrinsic clonality reflects a fundamental, previously unrecognized property of the immune system which challenges the view that TCR diversity declines primarily through passive erosion. Rather, TCR diversity emerges as a system level property mediated by repertoire size and intrinsic clonality, both of which are likely subject to homeostatic regulation. These findings offer a new conceptual framework for understanding TCR diversity within immune homeostasis which may guide therapies aimed at restoring immune function.