Abstract
Abstract Type 1 diabetes (T1D) is an autoimmune disorder that mediates destruction of insulin-producing pancreatic cells. Previous genetic association studies reported HLA II to be the major factor for increased susceptibility to T1D. Yet, knowledge remained limited on disease mechanism in Japanese. The purpose of current study is to elucidate immunological mechanism of risk and protective alleles and to determine the peptide binding repertoire of T1D susceptible DR alleles in the Japanese for Zinc Transporter 8 (ZnT8), one of the established auto-antigenic peptides. We expressed DR9 (DRA*01:01-DRB1*09:01), DR4(DRA*01:01-DRB1*04:05), DR8 (DRA*01:01-DRB1*08:02) contributing to susceptibility to T1D in the Japanese and DR15 (DRA1*01:01-DRB1*15:01) that are associated with protection in mammalian cells. A plate based peptide binding assay system was established using nickel coated microtiter plates to measure the binding of synthetic peptides to recombinant DR proteins. Established DR9 binding motif was searched in ZnT8 sequences. Binding characteristics of risk and protective DR allele products including DR9 are examined in utilization of a 20mer ZnT8 peptide library.
Published Version
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