Heterogeneity of T-cell receptor usage in experimental autoimmune neuritis in the Lewis rat

Brain. 1999 Mar;122 ( Pt 3):523-35. doi: 10.1093/brain/122.3.523.

Abstract

In experimental autoimmune neuritis (EAN), T-cell receptor (TCR) variable (V)-region gene usage by neuritogenic T cells has been reported to be clonally restricted at the RNA level. This study was designed to verify TCR usage by neuritogenic T cells at the protein level. We generated two monoclonal antibodies (mAbs) 7H4 and 8G8 specific for a Vbeta4/Valpha11 associated idiotype expressed by the majority of neuritogenic cells of P2-specific T-cell lines. The remaining neuritogenic P2-specific T cells either exhibited a dominant usage of the TCR Vbeta13 chain recognized by the recently generated mAbs 17D5 and 18B1 or showed diverse Vbeta usage. Treatment of adoptive-transfer (AT)-EAN or of EAN actively induced with the neuritogenic P2 peptide by mAbs 7H4 and 8G8 led to a partial, but significant, reduction of clinical disease. Treatment with Vbeta13-specific mAb 17D5 had no clear effect on active EAN. Our data show that at least three different TCR are used by P2-specific pathogenic T cells in EAN, an animal model for human inflammatory neuropathies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Amino Acid Sequence
  • Animals
  • Antibodies
  • Antibodies, Monoclonal / pharmacology
  • Antibody Specificity
  • Cell Line
  • Epitopes
  • Female
  • Genes, T-Cell Receptor*
  • Genetic Heterogeneity
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Neuritis, Autoimmune, Experimental / genetics*
  • Neuritis, Autoimmune, Experimental / immunology
  • Neuritis, Autoimmune, Experimental / therapy
  • Precipitin Tests
  • RNA / genetics
  • RNA / isolation & purification
  • Rats
  • Rats, Inbred Lew
  • Receptors, Antigen, T-Cell, alpha-beta / genetics*
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Antibodies
  • Antibodies, Monoclonal
  • Epitopes
  • Receptors, Antigen, T-Cell, alpha-beta
  • RNA

Associated data

  • GENBANK/AF054144
  • GENBANK/AF054145
  • GENBANK/AF054146
  • GENBANK/AF054147
  • GENBANK/AF054148
  • GENBANK/AF054149