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Virus-induced diabetes in a transgenic model: Role of cross-reacting viruses and quantitation of effector t cells needed to cause disease

Academic Article
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Overview

authors

  • Sevilla, N.
  • Homann, D.
  • von Herrath, M.
  • Rodriguez, F.
  • Harkins, S.
  • Whitton, J. Lindsay
  • Oldstone, Michael

publication date

  • April 2000

journal

  • Journal of Virology  Journal

abstract

  • 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.

subject areas

  • Amino Acid Sequence
  • Animals
  • Antigens, Viral
  • Base Sequence
  • Cercopithecus aethiops
  • Cross Reactions
  • DNA Primers
  • Diabetes Mellitus, Type 1
  • Disease Models, Animal
  • Lymphocytic choriomeningitis virus
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Sequence Homology, Amino Acid
  • T-Lymphocytes
  • Vero Cells
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Identity

International Standard Serial Number (ISSN)

  • 0022-538X

Digital Object Identifier (DOI)

  • 10.1128/jvi.74.7.3284-3292.2000

PubMed ID

  • 10708445
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Additional Document Info

start page

  • 3284

end page

  • 3292

volume

  • 74

issue

  • 7

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