Abstract
We determined that, over a biologic time interval, from 4 to 8 weeks of age, female non-obese diabetic (NOD) mice develop antibodies against pancreatic beta-cell-surface antigens depending upon the presence of both the MHC class II susceptibility allele, I-A(g7), and other NOD background genes. We generated a mAb from a pre-diabetic NOD mouse that binds to the surface of insulinoma cells and isolated mouse beta cells, and identified the target as a retroviral envelope glycoprotein expressed on pancreatic beta cells. The cloned and expressed sequence for this protein was recognized by the mAb. The antibody as well as sera from pre-diabetic NOD mice recognized the recombinant protein. Spontaneous T cell reactivity against a peptide from the cloned protein was found in NOD mice. In conclusion, a beta cell retroviral envelope protein is a target antigen that is selected by the NOD mouse immune system early in the pathogenesis of autoimmune diabetes.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adoptive Transfer
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Amino Acid Sequence
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Animals
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Antibodies, Monoclonal / immunology
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Antibody Specificity / immunology
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Autoantibodies / genetics
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Autoantibodies / immunology*
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Autoantibodies / metabolism
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Autoantigens / genetics
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Autoantigens / immunology
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Autoantigens / isolation & purification
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B-Lymphocytes / immunology
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Blotting, Western
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CD4-Positive T-Lymphocytes / drug effects
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism
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Cell Line, Tumor
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Clone Cells / immunology
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Cloning, Molecular
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Diabetes Mellitus, Type 1 / genetics
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Diabetes Mellitus, Type 1 / immunology*
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Female
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Flow Cytometry
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Gas Chromatography-Mass Spectrometry
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Gene Expression
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Histocompatibility Antigens Class II / immunology
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Histocompatibility Antigens Class II / metabolism
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Islets of Langerhans / chemistry
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Islets of Langerhans / immunology*
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Kinetics
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Lymphocyte Activation / immunology
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Male
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Mice
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Mice, Inbred NOD
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Mice, SCID
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Molecular Sequence Data
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Peptide Library
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Peptides / immunology
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Peptides / metabolism
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Peptides / pharmacology
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Precipitin Tests
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Protein Binding / immunology
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Retroviridae Proteins / genetics
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Retroviridae Proteins / immunology*
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Retroviridae Proteins / isolation & purification
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Reverse Transcriptase Polymerase Chain Reaction
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Sequence Alignment
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Viral Envelope Proteins / genetics
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Viral Envelope Proteins / immunology
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Viral Envelope Proteins / isolation & purification
Substances
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Antibodies, Monoclonal
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Autoantibodies
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Autoantigens
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Histocompatibility Antigens Class II
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Peptide Library
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Peptides
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Retroviridae Proteins
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Viral Envelope Proteins