Figure 1
Figure 1. HLA-DPB1 FD scores. (A) Schematic representation of the peptide antigen-binding groove encoded by HLA-DPB1*09:01 and definition of FDAA, FDAllele, and ΔFD scores. In the HLA-DPB1*09:01 molecule, the positions and side chains of 10 polymorphic AA residues used for the determination of FDAA scores are listed in boldface. The primary data for the development of FDAA and FDAllele scores were published previously.32 Briefly, 10 AA residues most relevant for peptide binding and/or TCR contact were selected, based on homology modeling and the available literature. Most of these AA residues are bimorphic (ie, only 2 different variants have been reported in the most frequent HLA-DPB1 alleles in Europeans),56 therefore only 1 variant with respect to WT HLA-DPB1*09:01 was analyzed. For two residues, namely at position 9 and 35, 3 different variants have been reported in the most frequent HLA-DPB1 alleles in Europeans,56 and both variants with respect to WT HLA-DPB1*09:01 were analyzed, for a total of 12 AA substitutions. FDAA scores for each of these 12 AAs were obtained as follows: the median RR of 17 clonal T-cell effectors allo-reactive to HLA-DPB1*09:01 as reference was experimentally determined and FDAA scores were then calculated as [1 – median RR]. The FDAllele score for individual HLA-DPB1 alleles, calculated as the sum of FDAA scores as shown in the figure, correlate well with TCE groups based on T-cell cross-reactivity patterns, and allow us to predict TCE group assignment for all known HLA-DPB1 alleles.32 (B) FDAllele scores of 19 HLA-DPB1 alleles occurring with a frequency of >0.5% in Europeans.56 TCE group assignment of the HLA-DPB1 alleles16,32,54 is shown on top.

HLA-DPB1 FD scores. (A) Schematic representation of the peptide antigen-binding groove encoded by HLA-DPB1*09:01 and definition of FDAA, FDAllele, and ΔFD scores. In the HLA-DPB1*09:01 molecule, the positions and side chains of 10 polymorphic AA residues used for the determination of FDAA scores are listed in boldface. The primary data for the development of FDAA and FDAllele scores were published previously.32  Briefly, 10 AA residues most relevant for peptide binding and/or TCR contact were selected, based on homology modeling and the available literature. Most of these AA residues are bimorphic (ie, only 2 different variants have been reported in the most frequent HLA-DPB1 alleles in Europeans),56  therefore only 1 variant with respect to WT HLA-DPB1*09:01 was analyzed. For two residues, namely at position 9 and 35, 3 different variants have been reported in the most frequent HLA-DPB1 alleles in Europeans,56  and both variants with respect to WT HLA-DPB1*09:01 were analyzed, for a total of 12 AA substitutions. FDAA scores for each of these 12 AAs were obtained as follows: the median RR of 17 clonal T-cell effectors allo-reactive to HLA-DPB1*09:01 as reference was experimentally determined and FDAA scores were then calculated as [1 – median RR]. The FDAllele score for individual HLA-DPB1 alleles, calculated as the sum of FDAA scores as shown in the figure, correlate well with TCE groups based on T-cell cross-reactivity patterns, and allow us to predict TCE group assignment for all known HLA-DPB1 alleles.32  (B) FDAllele scores of 19 HLA-DPB1 alleles occurring with a frequency of >0.5% in Europeans.56  TCE group assignment of the HLA-DPB1 alleles16,32,54  is shown on top.

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