TCR diversity and Treg cells, sometimes more is more.

Treg cells are critical for the maintenance of immune homeostasis and suppression of naturally occurring self-reactive T cells; however, in order to induce suppression Treg cells must first be activated via their T-cell receptor by recognition of specific antigen-MHC complexes. In this issue of the European Journal of Immunology, Föhse et al. [Eur. J. Immunol. 2011. 41: 3101-3113.] shed light on the important question of the role of TCR diversity on Treg-cell function by demonstrating that high TCR diversity is crucial for optimal Treg-cell expansion, peripheral reshaping of the Treg-cell TCR repertoire and in vivo suppressive capacity. In this Commentary, we discuss these findings and also propose a simple mathematical model to aid in the understanding of the relationship between Treg-cell TCR diversity and the level of suppression delivered by Treg cells in vivo.