Table 5.
IEDB-predicted binding of FVIII peptides to an HLA class II allele reference set
| IEDB percentile rank, % | |||||||
|---|---|---|---|---|---|---|---|
| HLA allele | WT | F2196A | F2196K | F2196L | M2199A | M2199W | M2199R |
| DRB1*01:01 | 6.87 | 13.70* | 15.40* | 13.04* | 11.97* | 10.95* | 11.55* |
| DRB1*03:01 | 16.60 | 18.81 | 18.81 | 9.61† | 16.6 | 19.22 | 19.22 |
| DRB1*04:01 | 2.32 | 6.65 | 6.65 | 4.78 | 4.20 | 5.34 | 7.80 |
| DRB1*04:05 | 4.58 | 22.26* | 15.75* | 6.09 | 8.21 | 18.55* | 15.58* |
| DRB1*07:01 | 4.21 | 4.21 | 4.21 | 2.39 | 4.10 | 4.14 | 4.03 |
| DRB1*08:02 | 6.00 | 5.81 | 5.95 | 5.05 | 8.78 | 8.78 | 5.15 |
| DRB1*09:01 | 0.94 | 2.18 | 2.18 | 1.97 | 1.21 | 1.61 | 1.88 |
| DRB1*11:01 | 5.04 | 11.79 | 11.79 | 9.49 | 9.49 | 10.04 | 8.25 |
| DRB1*12:01 | 19.66 | 26.08 | 26.08 | 13.79 | 18.40 | 26.12 | 21.62 |
| DRB1*13:02 | 38.79 | 34.21 | 41.41 | 25.8 | 39.01 | 39.11 | 38.97 |
| DRB1*15:01 | 18.10 | 22.85 | 22.85 | 10.98 | 18.64 | 12.23 | 18.64 |
| DRB3*01:01 | 8.08 | 11.50* | 9.71 | 14.09* | 4.92 | 12.11* | 10.21* |
| DRB3*02:02 | 8.64 | 8.64 | 8.64 | 8.64 | 12.31* | 8.54 | 10.02* |
| DRB4*01:01 | 21.82 | 21.82 | 21.82 | 21.82 | 21.82 | 21.82 | 21.82 |
| DRB5*01:01 | 2.34 | 4.69 | 4.69 | 3.86 | 4.69 | 2.24 | 4.69 |
| DQA1*05:01/DQB1*02:01 | 18.27 | 26.97 | 47.89 | 24.05 | 21.10 | 27.65 | 30.94 |
| DQA1*05:01/DQB1*03:01 | 16.93 | 15.87 | 16.85 | 14.85 | 16.93 | 16.93 | 16.93 |
| DQA1*03:01/DQB1*03:02 | 18.96 | 15.01 | 22.61 | 18.98 | 7.86† | 19.21 | 21.68 |
| DQA1*04:01/DQB1*04:02 | 10.25 | 16.25 | 20.51 | 13.13 | 10.25 | 10.25 | 10.25 |
| DQA1*01:01/DQB1*05:01 | 5.64 | 16.23* | 43.15* | 13.43* | 6.89 | 0.66 | 10.95* |
| DQA1*01:02/DQB1*06:02 | 11.91 | 4.87† | 12.38 | 9.18† | 11.91 | 11.91 | 11.91 |
| DPA1*02:01/DPB1*01:01 | 7.77 | 9.05 | 27.15* | 12.90* | 7.77 | 7.77 | 7.77 |
| DPA1*01:03/DPB1*02:01 | 0.96 | 1.68 | 3.90 | 1.43 | 2.13 | 1.71 | 0.65 |
| DPA1*01/DPB1*04:01 | 0.66 | 0.79 | 1.02 | 0.81 | 2.14 | 0.02 | 0.30 |
| DPA1*03:01/DPB1*04:02 | 13.93 | 20.86 | 27.97 | 12.32 | 29.03 | 14.60 | 20.61 |
| DPA1*02:01/DPB1*05:01 | 8.18 | 14.02* | 12.45* | 19.14* | 14.44* | 19.94* | 13.74* |
| DPA1*02:01/DPB1*14:01 | 10.89 | 23.13 | 21.84 | 13.05 | 11.25 | 16.11 | 9.36† |
Predicted binding of WT and sequence-modified 15-mer peptides spanning FVIII2182-2213 to the IEDB HLA class II reference set, which consists of the most frequent MHCII (HLA class II) loci worldwide representing 46% of DRB1, 77% of DRB3/4/5, 57% of DQA1/DQB1, and 76% of DPA1/DPB1 alleles.63 The highest predicted peptide affinity (lowest percentile rank) score for each MHCII is listed. Predictions were generated using the “recommended IEDB method,” which defaults to the IEDB consensus method when combined consensus scores are possible.36,37 The consensus method was not applicable to the DRB1*12:01, DRB3*02:02, and DPA1*02:01/DPB1*14:01 alleles, thus these predictions were generated by the SMM-align, NetMHCIIpan, and NetMHCIIpan algorithms, respectively. Interactions predicted to be in the top 10% of possible peptide affinities for the indicated MHCII are bolded. A threshold of 10% is recommended by IEDB for predicting potential physiologically relevant binding interactions. Percentile ranks (predicted affinities) of the sequence-modified FVIII peptides (columns 3-8) were compared with those of the WT FVIII peptides (column 2).
Substitutions predicted to decrease the peptide affinity for a particular MHCII to below the top 10%, and in which the affinity of the WT peptide ranks in the top 10%, indicating that this substitution may decrease immunogenicity restricted to this allele.
Substitutions predicted to increase the peptide affinity for a particular MHCII to within the top 10%, and in which the affinity of the WT peptide ranks below the top 10%, indicating that this substitution may create a neoepitope restricted to this allele.