Autoantibodies and CD4 T cells target a beta cell retroviral envelope protein in non-obese diabetic mice.
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.
Levisetti
Matteo G
MG
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA.
Suri
Anish
A
Vidavsky
Ilan
I
Gross
Michael L
ML
Kanagawa
Osami
O
Unanue
Emil R
ER
D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D001323:Autoantibodies / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001324:Autoantigens / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D001402:B-Lymphocytes / Q000276:immunology; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D002999:Clone Cells / Q000276:immunology; D003001:Cloning, Molecular; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D008401:Gas Chromatography-Mass Spectrometry; D015870:Gene Expression; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D007515:Islets of Langerhans / Q000737:chemistry / Q000276:immunology*; D007700:Kinetics; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008969:Molecular Sequence Data; D019151:Peptide Library; D010455:Peptides / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D011233:Precipitin Tests; D011485:Protein Binding / Q000276:immunology; D012191:Retroviridae Proteins / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D001324:Autoantigens; D000949:Histocompatibility Antigens Class II; D019151:Peptide Library; D010455:Peptides; D012191:Retroviridae Proteins; D014759:Viral Envelope Proteins