The HLA-DQβ₁ chain contains an aspartic acid (Asp) at position 57 in most people; in Caucasoid populations, patients with IDDM more often have valine, serine, or alanine at this position instead, as well as other differences. Asp 57, shown in red on the backbone structure of the DQβ chain, forms a salt bridge (shown in green in the center panel) to an arginine residue (shown in pink) in the adjacent α chain (gray). The change to an uncharged residue (for example, alanine, shown in yellow in the bottom panel) disrupts this salt bridge, altering the stability of the DQ molecule. The nonobese diabetic (NOD) strain of mice, which develops spontaneous diabetes, shows a similar replacement of serine for aspartic acid at position 57 of the homologous I-Aβ chain, and NOD mice transgenic for β chains with Asp 57 have a marked reduction in diabetes incidence. Photographs courtesy of C. Thorpe.