IngentaConnect Endogenous Ecotropic Murine Leukemia Viral (MuLV) Envelope Protei...

Authors: Choi S-E.¹; Kim K-S.¹; Kim K-H.¹; Choi U-Y.²; Kim H-M.³; Yoon J-W.^{1, 4}; Kang Y.¹

Source: Journal of Autoimmunity, Volume 15, Number 3, November 2000 , pp. 347-357(11)

Abstract:

The identification and characterization of autoantigens associated with autoimmune IDDM (insulin dependent diabetes mellitus) would help to elucidate the pathogenic mechanism of this disease as well as to design antigen-based immunotherapy. Non-obese diabetic (NOD) mice have been used as the best model for studying the pathogenesis of human IDDM. To identify new autoantigens associated with IDDM, the lambda gt11-cDNA library from MIN6N8a, NOD-derived pancreatic beta cell line, was constructed and then candidate autoantigen clones were screened with prediabetic NOD sera. Nine positive clones were selected from 2×10⁵phage plaques. The nucleotide sequencing and homology searching showed that six of the nine positive clones had part of the endogenous ecotropic murine leukemia viral (MuLV) envelope gene. Nested deletion of this envelope gene revealed that the leucine zipper region in the transmembrane domain of MuLV envelope protein was the target epitope(s) reactive with prediabetic NOD mice sera. The prevalence of MuLV envelope protein-positive antibody in NOD mice was around 46%, while the non-NOD mice strains including BALB/c, ICR, C57BL/6, and SJL/J mice did not produce this envelope protein-reactive antibody. The expression of endogenous ecotropic MuLV envelope gene in NOD mouse pancreas was distinct in those with severe insulitis. However, both prediabetic and diabetic NOD mice did not show the MHC class II-restrictive cellular autoimmunity against our purified recombinant envelope protein. In this study, we showed that the endogenous ecotropic MuLV envelope protein was a new autoantigen reactive with the activated NOD humoral immune system. Copyright 2000 Academic Press

Language: English

Document Type: Research article

Affiliations: 1: Laboratory of Endocrinology, Institute for Medical Science, Ajou University School of Medicine, Suwon, Kyunggi-do, Korea 2: Department of Genetic Engineering, Hallym University, Chunchon, Kangwon-do, Korea 3: Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Kyunggi-do, Korea 4: Laboratory of Viral Immunopathogenesis of Diabetes, Julia McFarlane Diabetes Research Center, Department of Microbiology and Infectious Disease, Faculty of Medicine, The University of Calgary, Calgary, Alberta, Canada

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Endogenous Ecotropic Murine Leukemia Viral (MuLV) Envelope Protein as a New Autoantigen Reactive with Non-obese Diabetic Mice Sera