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Journal of Virology, April 2000, p. 3284-3292, Vol. 74, No. 7
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Virus-Induced Diabetes in a Transgenic Model: Role of Cross-Reacting Viruses and Quantitation of Effector T Cells Needed To Cause Diseasedagger

Noemi Sevilla, Dirk Homann, Matthias von Herrath, Fernando Rodriguez, Stephanie Harkins, J. Lindsay Whitton, and Michael B. A. Oldstone*

Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037

Received 2 December 1999/Accepted 4 January 2000

Virus-specific cytotoxic T lymphocytes (CTL) at frequencies of >1/1,000 are sufficient to cause insulin-dependent diabetes mellitus (IDDM) in transgenic mice whose pancreatic beta  cells express as "self" antigen a protein from a virus later used to initiate infection. The inability to generate sufficient effector CTL for other cross-reacting viruses that fail to cause IDDM could be mapped to point mutations in the CTL epitope or its COO- flanking region. These data indicate that IDDM and likely other autoimmune diseases are caused by a quantifiable number of T cells, that neither standard epidemiologic markers nor molecular analysis with nucleic acid probes reliably distinguishes between viruses that do or do not cause diabetes, and that a single-amino-acid change flanking a CTL epitope can interfere with antigen presentation and development of autoimmune disease in vivo.

* Corresponding author. Mailing address: Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037. Phone: (858) 784-8054. Fax: (858) 784-9981. E-mail: mbaobo{at}scripps.edu.

dagger This is publication no. 11201-NP from the Department of Neuropharmacology, The Scripps Research Institute, La Jolla, Calif.

Journal of Virology, April 2000, p. 3284-3292, Vol. 74, No. 7
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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