An effective way of visualizing the receptor-binding motif is by using sequence logos. Sequence logos were introduced by Schneider and Stephens14 to graphically represent the sequence motif contained in a set of aligned sequences, where at each position, the frequency of all amino acids is displayed as a stack of letters. The height of a column in the logo is given as the information content in bits of the alignment at that particular position, and the relative height of individual letters is proportional to the frequency of the corresponding amino

acid at that position. SRT1720 order In this paper, we use such sequence logos to display the HLA-DP and HLA-DQ binding specificities identified by NNAlign. The five HLA-DP allelic variants were chosen by Wang et al.7 to cover a high percentage of the human population. Only considering the β-chain, more polymorphic than the α-chain and the main determinant for HLA-DP binding,15,16 the allele choice provides coverage of about 92% of the average population at the DPB1 locus.9 The sequence motifs identified by NNAlign for the five HLA-DP molecules are shown in Fig. 1. In general, all variants share a common pattern characterized by anchors at positions P1 and P6, with strong preferences for phenylalanine (F) and

other aromatic or hydrophobic amino acids. Additionally, some molecules appear to Selleckchem Metabolism inhibitor have a hydrophobic Oxalosuccinic acid preference at P9 especially for leucine (L). This P9 anchor was previously described for DPB1*04:02,17 but here we observe it also

for other variants such as DPA1*02:01-DPB1*01:01 and DPA1*02:01-DPB1*05:01. In some instances, and notably for DPA1*03:01-DPB1*04:02, the residues at position P7 appear to have influence on the binding specificity of the molecule. This has not been described in previous reports. Another small exception to the P1–P6 hydrophobic/aromatic pattern is observed in the allelic variant DPA1*02:01-DPB1*05:01, where the positively charged amino acids R and K are moderately preferred at P1 together with hydrophobic ones, as was also previously noted.9 Taken as a whole, there appears to be a large overlap in the peptide-binding specificities of the five DP molecules, characterized by strong hydrophobic/aromatic anchors at P1 and P6, with the few exceptions noted above. Consistent with these observations, previous studies have found considerable overlaps in the peptide repertoires that can bind different DP alleles, and suggested the existence of a DP supertype encompassing the most common variants.9,17 Greenbaum et al.,18 on the basis of shared binding repertoires, suggested the presence of two DP supertypes: a ‘main DP’ supertype (composed of DPB1*01:01, 05:01 and 04:02) and a DP2 supertype (DPB1*02:01 and 04:01).