Figure 6.

Improved self representation during negative selection allows self-foreign discrimination. (A) self peptides from large clusters delete the same TCRs as their neighbors and are thus exchangeable during negative selection, whereas peptides from small clusters are not; (B) percentage of self-reactive TCRs deleted by optimal training sets of self peptides during negative selection. TCR deletion with random training sets was computed on the data from Figure 5E for comparison; (C) peptide exchangeability distribution in the full set of all self peptides compared to that in random and optimal subsets of 100,000 peptides. Exchangeability is defined as the number of self neighbors + 1; (D) self-HIV discrimination after selection on optimal training sets. Discrimination after selection on random training sets (Figure 5D) is shown for comparison. See also Figure S4; (E) percentage of self peptides with HIV neighbor(s) plotted against exchangeability (self peptides were divided into 10 equal-number deciles from low to high exchangeability). Negative selection in panels b and d was performed with t = 4, and results were plotted as mean ± SEM of 30 simulations.