Analysis of the H-bond network in the pocket 7, the peptide binding pocket where the HLA-DR residue β47 is mapping, of HLA-DR molecules carrying HLA-DRPhe47 (Panel A: HLA-DR3 and Panel B: HLA-DR15) or its counterpart Tyr47 (Panel C: HLA-DR1 and Panel D: HLA-DR4). Molecular modelling of the PDB entry crystal structures (HLA-DR3: 1A6A; HLA-DR15: 1BX2; HLA-DR1: 1AQD; HLA-DR4: 2SEB) have been evaluated with the SwissPDB viewer v3.7b2 software (free available at http://ca.expasy.org/spdbv/). The HLA-DR α-chain backbone is reported in red colored ribbon style, while the HLA-DR β-chain backbone is reported in grey colored ribbon. Aminoacids are colored in CPK style (C: light blue; O: red; N: blue) and residue names are reported in red. H-bonds were computed with the SwissPDB viewer (H-bond detection threshold: 1.20–2.76 A when Hydrogen is present and 2.19–3.30 A when Hydrogen is absent) and are shown as green dashed lines. All the aminoacids presenting electron donor groups in the pocket 7, of HLA-DR1, -DR3, -DR4 and -DR15, putatively capable of coordinating Be are shown (residues α69, β28, β61, β70 and β71). In the HLA-DR3 crystal structure (Panel A) with the presence of Phe47 only one of the two terminal oxygens of Aspβ28 is engaged in a H-bond network with Lys71, leaving four other contacts points for co-ordinating Be (specifically residues αAsn69, βAsp28, βTrp61, βGln70). A similar pattern is present in HLA-DR15 (Panel B) where, with the presence of Phe47, no H-bonds are present leaving 5 electron donor groups available for Be coordination (specifically one electron donor group for each residue αAsn69, βTrp61, βGln70 and two electron donor groups for βAsp28). When Tyr47, the HLA-DRPhe47 counterpart, is present in HLA-DR molecules as in HLA-DR1 (panel C) and HLA-DR4 (Panel D), the H-bond network of pocket 7 results dramatically modified. Specifically, Tyr47 engages in a H-bond network with residues Asp28 and Arg71 in HLA-DR1 (Panel C) or Asp28 and Lys71 in HLA-DR4 (Panel D). As a consequence there is reduced availability of electron donor groups capable to coordinate Be.