Figure 7.

Thymic enrichment for rare AAs facilitates self-foreign discrimination by improving self representation during negative selection. (A) exchangeability versus peptide AA frequency score in a random sample of 1000 self peptides (frequency score is low for peptides with many rare AAs (detailed methods in Appendix A)). Pearson’s correlation coefficient r = 0.716, with 95% confidence interval [0.684, 0.745]. See also Figure S5; (B) discrimination after negative selection on self peptides chosen with a (weak/strong) bias for rare AAs. Discrimination after selection on random peptides (Figure 5D) is included for comparison. Plots show self-HIV discrimination (left), and self-other self discrimination (right, where a random sample of self was assigned the label “foreign” before selection on training sets from the remaining “self” peptides); (C) self-foreign discrimination for different pathogens after negative selection on 150,000 self peptides chosen randomly or with AA bias. See Figure S6 for the full discrimination curves. Negative selection in panels b and c was performed with t = 4, and results were plotted as mean ± SEM of 30 simulations.