Table 4.
ProPred-predicted binding of FVIII peptides to 51 HLA-DR alleles
| FVIII peptide | 1% Threshold | 3% Threshold | 10% Threshold |
|---|---|---|---|
| WT | 04:05,* 04:08 | 01:01, 01:02, 04:01, 04:04, 04:05, 04:08, 04:21, 04:23, 04:26, 08:13, DRB5*01:01, DRB5*01:05 | 30 HLA-DR |
| F2196A | None | None | 15 HLA-DR |
| F2196K | None | None | 15 HLA-DR |
| F2196L | 04:04,† 04:08, 04:23 | 01:02, 04:02, 04:04, 04:05, 04:08, 04:10, 04:23, 08:13 | 42 HLA-DR |
| M2199A | None | 01:01, 04:08 | 26 HLA-DR |
| M2199W | None | 04:01, 04:02, 04:08, DRB5*01:01, DRB5*01:05 | 22 HLA-DR |
| M2199R | 08:13 | 08:02, 08:13 | 20 HLA-DR |
The input sequences for the ProPred algorithm were WT and sequence-modified FVIII2182-2213, which spans all possible 15-mer sequences that include the substitution sites at F2196 or M2199. ProPred predicts binding to 49 different HLA-DRB1 alleles and 2 HLA-DRB5 alleles.35 Interactions with predicted affinities in the top 1%, 3%, and 10% for each HLA-DR are listed. The predicted highest-affinity interactions are in the 1% threshold column. A threshold stringency of 3% is recommended to predict potential physiologically relevant binding affinities. “None” indicates that no HLA-DR were predicted to bind this FVIII peptide at or above the indicated affinity threshold. At the least-stringent affinity threshold (top 10%), the number of HLA-DRs predicted to bind 1 or more motifs within FVIII2182-2213 is listed for the WT sequence and for the 6 modified sequences.
Four-digit numbers correspond to HLA-DRB1* alleles, unless an HLA-DRB5* allele is specified.
Bolded allele numbers indicate that the amino acid substitution is predicted to result in binding (at this threshold level) that was not predicted for the corresponding WT FVIII sequence. Such high-affinity MHCII binding could create neoepitopes restricted to these alleles.