Crystal structure of an HLA-DP2 heterodimer in complex with a self-peptide. The HLA-DPα chain is shown in yellow, and the HLA-DPβ chain is shown in blue. Shown in red is the P1 pocket formed in part by residue 31 of the α chain and residues 85 to 87 of the β chain. The self-peptide filling the gap between the α helices of the heterodimer is shown in green. HLA-DP2 is a heterodimer encoded by DPA1*0103 and DPB1*0201 with M at position 31 of the α chain and GPM at positions 85 to 87 of the β chain. The hydrophobic aromatic side chain of phenylalanine at the P1 anchor position of the peptide projects into the hydrophobic M∼GPM P1 pocket. Substitution of Q for M at position 31 in the α chain would replace a hydrophobic residue with a more hydrophilic residue. This substitution would not alter the overall structure of the heterodimer but would change the P1 anchor residues that fit the pocket and the repertoire of peptides that can be presented. The crystal structure of an HLA-DPB1 heterodimer with a Q∼GPM P1 pocket has not been determined. The structure shown in the figure was rendered with PyMOL (The PyMOL Molecular Graphics System, version 1.7.4.4, Schrödinger, LLC.).