A shared TCR CDR3 sequence in NOD mouse autoimmune diabetes

Int Immunol. 1999 Jun;11(6):951-6. doi: 10.1093/intimm/11.6.951.

Abstract

T cells involved in autoimmune diseases have been characterized by the genetic elements used to construct their autoimmune TCR. In the present study, we sequenced the alpha and beta chains of the TCR expressed by a CD4(+) T cell clone, C9, functional in NOD mouse diabetes. Clone C9 can adoptively transfer diabetes or, when attenuated, C9 can be used to vaccinate NOD mice against diabetes. Clone C9 recognizes a peptide epitope (p277) of the 60 kDa heat shock protein (hsp60) molecule. We now report that the C9 TCR beta chain features a CDR3 peptide sequence that is prevalent among NOD mice. This CDR3 element is detectable by 2 weeks of age in the thymus, and later in the spleen and in the autoimmune insulitis. Thus, a TCR CDR3beta sequence appears to be a common idiotope associated with mouse diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / metabolism
  • Cell Line
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / metabolism
  • Female
  • Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor
  • Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
  • Humans
  • Male
  • Mice
  • Mice, Inbred NOD
  • Molecular Sequence Data
  • Organ Specificity / genetics
  • Organ Specificity / immunology
  • Receptors, Antigen, T-Cell, alpha-beta / biosynthesis
  • Receptors, Antigen, T-Cell, alpha-beta / genetics*
  • Spleen / chemistry
  • Spleen / immunology
  • Spleen / metabolism

Substances

  • Receptors, Antigen, T-Cell, alpha-beta