Systematic analysis of differences between protective and nonprotective MHC-I alleles. (A) Relative fitness scores of mutations in indicated epitopes. Epitopes shown as examples are SL9 (Gag positions 77 to 85), KF11 (Gag positions 163 to 173), TW10 (Gag positions 240 to 249), and KK10 (Gag positions 263 to 272). (B) Relative fitness scores of mutations in epitopes presented by protective or nonprotective MHC-I alleles. A total of 559 mutations in the epitopes targeted by protective MHC-I alleles and a total of 550 mutations targeted by nonprotective MHC-I alleles were analyzed. (C) MHC-I binding affinity changes of mutations in epitopes presented by protective or nonprotective MHC-I alleles were compared. A total of 1,401 mutations in the epitopes targeted by protective MHC-I alleles and a total of 1,325 mutations in the epitopes targeted by nonprotective MHC-I alleles were analyzed. (D) The correlation between predicted ranking of MHC-I protectiveness and ranking calculated based on TIHIVC study data. Predicted ranking was fitted by a linear regression model using the average effect of mutations on relative fitness scores and MHC-I binding affinity as variables (Spearman correlation, 0.63; P = 0.003).