Figure 3. Treg formation in a modified avidity model of thymocyte development.
The avidity model of thymocyte development holds that the strength of the TCR signal determines whether a developing thymocyte undergoes death by neglect, positive selection, or deletion. The outcome of these different TCR signals is typically presented as a bell-shaped curve, in which the recovery of thymocytes is plotted against the amount of peptide [or, by extension, the avidity of the interaction with self-peptide(s)], which is encountered by the thymocyte. One idea has been that Treg formation might be promoted by TCR signaling that is below a threshold for overt deletion (A). However, our data are more consistent with a model in which the strength of the TCR signal necessary to induce deletion and Treg formation overlaps (B). As represented in the figure, this model is based on the finding that 6.5hi thymocytes undergo increasing deletion in response to higher amounts of HA mRNA in the different TS1 × HA lineages, and among the cells that evade deletion, similar proportions become Tregs.