A hierarchy of T cell receptor motifs determines responsiveness to the immunodominant epitope in experimental autoimmune myasthenia gravis

J Neuroimmunol. 2003 Dec;145(1-2):68-76. doi: 10.1016/j.jneuroim.2003.09.007.

Abstract

The predominant murine T lymphocyte population responding to Talpha146-162, the immunodominant epitope in EAMG, expresses the TCRBV 6 gene segment. However, cells expressing other TCRBV gene segments also react with this peptide. In order to more precisely characterize the Talpha146-162-specific TCR repertoire, we isolated CD4high cells from peptide-immunized mice. The majority of CD4high cells utilized an acidic TCR beta chain CDR3 motif regardless of TCRBV gene usage. Analysis of T cell clones demonstrated a fourfold higher avidity of Vbeta6+ than non-Vbeta6 cells for Talpha146-162 indicating that a hierarchy of TCR motifs determines T cell responsiveness in EAMG.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / pathology
  • Cell Division / immunology
  • Clone Cells
  • Complementarity Determining Regions / biosynthesis
  • Epitopes, T-Lymphocyte / administration & dosage*
  • Epitopes, T-Lymphocyte / biosynthesis
  • Epitopes, T-Lymphocyte / genetics
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor
  • Immunodominant Epitopes / administration & dosage*
  • Immunodominant Epitopes / biosynthesis
  • Immunodominant Epitopes / genetics
  • Immunodominant Epitopes / immunology
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Myasthenia Gravis, Autoimmune, Experimental / immunology*
  • Myasthenia Gravis, Autoimmune, Experimental / pathology
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / immunology
  • Receptors, Antigen, T-Cell, alpha-beta / administration & dosage*
  • Receptors, Antigen, T-Cell, alpha-beta / biosynthesis
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocyte Subsets / pathology

Substances

  • Complementarity Determining Regions
  • Epitopes, T-Lymphocyte
  • Immunodominant Epitopes
  • Peptide Fragments
  • Receptors, Antigen, T-Cell, alpha-beta