Mapping of autoantibody epitopes of the novel tetraspanin 7 autoantigen relevant in type I diabetes

Kraus, Gloria (2016) Mapping of autoantibody epitopes of the novel tetraspanin 7 autoantigen relevant in type I diabetes. Diploma thesis, Faculty of Science > Department of Biology.

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Abstract

Type 1 diabetes mellitus (T1DM) is an organ-specific autoimmune disease, which is characterized by a deficiency in endogenous pancreatic insulin production. The typical biomarkers that predict type I diabetes are serum autoantibodies against beta-cell antigens: insulin, GAD65, IA2, and ZnT8. Along with the four known autoantigens, autoantibodies were also detected to another potential autoantigen, a 38 kDa glycosylated membrane protein known as Glima 38. Glima 38 was later identified as tetraspanin 7 (TSPAN7). TSPAN7 is a member of the tetraspanin protein family, it has seven domains: three cytoplasmic (C1 to C3), four transmembrane (TM1 to TM4), and two extracellular (E1 and E2), and in pancreas it is found specifically in the islets of Langerhans. Hypothesis of this study is that by using luciferase immunoprecipitation systems (LIPS) assay, binding of autoantibodies to TSPAN7 protein fragments can be observed and quantified. The aim of this study was to map autoepitopes of the TSPAN7 in order to provide a more detailed description of autoimmune responses in T1DM individuals. The main method was the luciferase immunoprecipitation systems (LIPS) assay, where nanoluciferase-tagged truncated TSPAN7 forms were tested against 41 serum samples that had autoantibodies against full-length TSPAN7 and 20 samples that did not have autoantibodies against full-length TSPAN7. The results suggest that E2 and C3 TSPAN7 domains are the most likely candidates that carry autoepitopes, and that TM4 could play a role in the binding as well, either by carrying autoepitopes, or by positioning E2 and C3 in the proper conformation.

Item Type: Thesis (Diploma thesis)
Keywords: type I diabetes mellitus, T1DM, tetraspanin 7, TSPAN7, autoantibodies, luciferase immunoprecipitation systems assay, LIPS, autoepitopes
Supervisor: Eugster, Anne
Co-supervisor: Korać, Petra
Date: 2016
Number of Pages: 45
Subjects: NATURAL SCIENCES > Biology
Divisions: Faculty of Science > Department of Biology
Depositing User: Grozdana Sirotic
Date Deposited: 19 Jan 2017 09:50
Last Modified: 19 Jan 2017 09:50
URI: http://digre.pmf.unizg.hr/id/eprint/5421

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