A stronger association with the DQB1 locus alone was reported when an allele-encoding aspartic acid at position β57 of DQB1 was found to be associated with resistance to type I diabetes, while an allele encoding a neutral residue, such as alanine or serine at position β57 conferred susceptibility. This molecule forms a critical residue in peptide-binding pocket nine (P9) of the DQB1-binding pocket involved in antigen presentation and T cell receptor interaction. Its carboxylate group forms a salt bridge with arginine at position α57 of DQA1 chain that stabilizes the heterodimer between the DQA1 and DQB1 chains. The presence of aspartat at this position could alter the stability of the molecule and/or antigen-presenting repertoire, thus making the molecule more prone to binding autoreactive antigens.
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