AsianScientist (Dec. 23, 2014) – The stability of important immune proteins plays a role in the development of autoimmune disease and could explain individual variability in immune responses, according to a study published in the Journal of Clinical Investigation.
Autoimmune diseases, such as type 1 diabetes, are elicited through undesired immunological reactions against healthy tissues or organs, which occur through misrecognition of healthy tissues or organs as in infected states or as foreign matters by immune molecules.
Genes encoding human leukocyte antigens (HLA) play a central role in the recognition of the immunological self and non-self. Although it is known that HLA gene polymorphism (variation between individuals) is strongly associated with a variety of autoimmune diseases including type 1 diabetes, the underlying mechanism has remained elusive.
In the present study, a research group led by Assistant Professor Hiroko Miyadera and Professor Katsushi Tokunaga at the University of Tokyo profiled protein stability of the diverse HLA allele products. They found that HLA alleles that are associated with susceptibility to type 1 diabetes encoded for extremely unstable HLA proteins.
In previous studies, the relation between HLA gene polymorphism and autoimmune disease has been attributed to the allelic differences of the HLA in the recognition of peptides, but the actual mechanism of pathogenesis remained unknown. The current study suggests that a fundamentally different process may operate in the development of autoimmune diseases. This finding provides a new clue to explore the mechanistic basis of autoimmunity.
The article can be found at: Miyadera et al. (2014) Cell-surface MHC Density Profiling Reveals Instability of Autoimmunity-Associated HLA.
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Source: University of Tokyo.
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