Cytoplasmic ends of tetraspanin 7 harbour epitopes recognised by autoantibodies in type 1 diabetes

Diabetologia
Anne EugsterE Bonifacio

Abstract

The beta cell protein tetraspanin 7 is a target of autoantibodies in individuals with type 1 diabetes. The aim of this study was to identify autoantibody epitope-containing regions and key residues for autoantibody binding. Autoantibody epitope regions were identified by immunoprecipitation of luciferase-tagged single or multiple tetraspanin 7 domains using tetraspanin 7 antibody-positive sera. Subsequently, amino acids (AAs) relevant for autoantibody binding were identified by single AA mutations. In tetraspanin 7 antibody-positive sera, antibody binding was most frequent to tetraspanin 7 proteins that contained the NH2-terminal cytoplasmic domain 1 (C1; up to 39%) or COOH-terminal C3 (up to 22%). Binding to C3 was more frequent when the domain was expressed along with the flanking transmembrane domain, suggesting that conformation is likely to be important. Binding to external domains was not observed. Single AA mutations of C3 identified residues Y246, E247 and R239 as critical for COOH-terminal binding of 9/10, 10/10 and 8/10 sera tested, respectively. Mutation of cysteines adjacent to the transmembrane domain at either residues C235 or C236 resulted in both decreased (8/178 and 15/178 individuals, respectively; >twofold de...Continue Reading

References

Sep 26, 1995·Proceedings of the National Academy of Sciences of the United States of America·N PassiniL Rogge
Nov 30, 2005·Nature Reviews. Molecular Cell Biology·Martin E Hemler
Mar 10, 2016·Diabetes·Kerry A McLaughlinMichael R Christie
May 26, 2016·Diabetologia·Denise WaltherEzio Bonifacio

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Citations

Aug 10, 2019·Clinical and Experimental Immunology·E Bonifacio, P Achenbach
Apr 22, 2020·Medical Microbiology and Immunology·Kerry A McLaughlinMichael R Christie

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