Pervasive and stochastic changes in the TCR repertoire of regulatory T-cell-deficient mice

We hypothesize that regulatory T-cell (Treg)-deficient strainshave an altered TCR repertoire in part due to the expansionof autoimmune repertoire by self-antigen. We compared the Vβfamily expression profile between B6 and Treg-lacking B6.Cg-Foxp3^sf/Y(B6.sf) mice using fluorescent anti-Vβ mAbs and observedno changes. However, while the spectratypes of 20 Vβ familiesamong B6 mice were highly similar, the Vβ family spectratypesof B6.sf mice were remarkably different from B6 mice and fromeach other. Significant spectratype changes in many Vβfamilies were also observed in Treg-deficient IL-2 knockout(KO) and IL-2R KO mice. Such changes were not observed withanti-CD3 mAb-treated B6 mice or B6 CD4⁺CD25^– T cells.TCR transgenic (OT-II.sf) mice displayed dramatic reductionof clonotypic TCR with concomitant increase in T cells bearingnon-transgenic Vβ and V families, including T cells withdual receptors expressing reduced levels of transgenic V andendogenous V. Collectively, the data demonstrate that Treg deficiencyallows polyclonal expansion of T cells in a stochastic manner,resulting in widespread changes in the TCR repertoire.