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Significance Central tolerance can generate holes in the CD4 T cell repertoire or divert cells into the Foxp3+ T regulatory (Treg ) cell lineage. Little is known with regard to how these diametrically different cell fate decisions of autoreactive cells shape the size and composition of polyclonal cohorts of antigen-specific T cells. Here we generated inventories of very rare autoreactive T cells in the naive versus tolerant polyclonal repertoire and identified T cell receptors (TCRs) that were lost, whereas others mediated Treg cell differentiation. The antigen responsiveness of these TCRs revealed a TCR hierarchy that not only separates deleted from diverted TCRs but also generates a Treg cell compartment with high antigen reactivity.

Inventories of naive and tolerant mouse CD4 T cell repertoires reveal a hierarchy of deleted and diverted T cell receptors