Diversity in HLA heterodimers

2014 Fiscal Year Final Research Report

• Project Area: HLA polymorphism, disease and evolution
• Project/Area Number: 22133006
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Research Institute, International Medical Center of Japan (2013-2014); The University of Tokyo (2010-2012)
• Principal Investigator: MIYADERA Hiroko 独立行政法人国立国際医療研究センター, その他部局等, その他 (40361464)
• Co-Investigator(Kenkyū-buntansha): HITOMI Yuki 東京大学, 大学院医学系研究科, 助教 (10525819)
• Project Period (FY): 2010-04-01 – 2015-03-31
• Keywords: ヒト白血球抗原(HLA) / 主要組織適合性抗原(MHC)

Outline of Final Research Achievements

Variations in human leukocyte antigens (HLA) are strongly associated with immune-related disorders including autoimmune diseases and infections, among others. However, underlying mechanism has remained elusive for most of HLA-associated diseases. In this study, we aimed to uncover the mechanism of HLA association with autoimmune and other HLA-associated disorders. We have established a protocol to estimate allelic differences in the protein stability of HLA. Using this method, we analyzed the stability of diverse HLA-DQ allele products and found that HLA-DQ alleles that are associated with susceptibility to type 1 diabetes encoded extremely unstable proteins. Our finding suggests that a novel mechanistic basis might operate in the development of autoimmune diseases.

Free Research Field

生化学、免疫遺伝学