TY - JOUR
T1 - Autoantibodies and CD4 T cells target a β cell retroviral envelope protein in non-obese diabetic mice
AU - Levisetti, Matteo G.
AU - Suri, Anish
AU - Vidavsky, Ilan
AU - Gross, Michael L.
AU - Kanagawa, Osami
AU - Unanue, Emil R.
N1 - Funding Information:
We want to thank Kevin Clark, Thomas Esparza, Gina Filley, Kathy Frederick, Shirley Petzold and Barbara Vaupel for their excellent technical support. We thank Marco Colonna and Marina Cella for their insights and help. This work was supported by grants from the National Institutes of Health and from the Kilo Diabetes and Vascular Research Foundation (St Louis, MO). M. G. L. was supported by a clinical investigator faculty award from the Howard Hughes Medical Institute to Washington University. The mass spectrometry was supported in part by the NCRR of the NIH (grant P41RR00954).
PY - 2003/12
Y1 - 2003/12
N2 - 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 β-cell-surface antigens depending upon the presence of both the MHC class II susceptibility allele, I-Ag7, 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 β cells, and identified the target as a retroviral envelope glycoprotein expressed on pancreatic β 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 β cell retroviral envelope protein is a target antigen that is selected by the NOD mouse immune system early in the pathogenesis of autoimmune diabetes.
AB - 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 β-cell-surface antigens depending upon the presence of both the MHC class II susceptibility allele, I-Ag7, 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 β cells, and identified the target as a retroviral envelope glycoprotein expressed on pancreatic β 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 β cell retroviral envelope protein is a target antigen that is selected by the NOD mouse immune system early in the pathogenesis of autoimmune diabetes.
KW - Autoimmunity
KW - Diabetes mellitus
KW - Ig
KW - Islets of langerhans
KW - T lymphocyte
UR - http://www.scopus.com/inward/record.url?scp=0346777311&partnerID=8YFLogxK
U2 - 10.1093/intimm/dxg143
DO - 10.1093/intimm/dxg143
M3 - Article
C2 - 14645156
AN - SCOPUS:0346777311
SN - 0953-8178
VL - 15
SP - 1473
EP - 1483
JO - International Immunology
JF - International Immunology
IS - 12
ER -