The Insulin-Specific T Cells of Nonobese Diabetic Mice Recognize a Weak MHC-binding Segment in More Than One Form

J Immunol. 2007 May 15;178(10):6051-7. doi: 10.4049/jimmunol.178.10.6051.

Abstract

Several naturally occurring anti-insulin CD4 T cells were isolated from islet infiltrates of NOD mice. In accordance with the results of others, these T cells recognized the segment of the beta-chain from residues 9-23. Peptides encompassing the B:(9-23) sequence bound weakly to I-Ag7 in two main contiguous registers in which two residues at the carboxyl end, P20Gly and P21Glu, influenced binding and T cell reactivity. Naturally occurring insulin-reactive T cells exhibited differing reactivities with the carboxyl-terminal amino acids, although various single residue changes in either the flanks or the core segments affected T cell responses. The insulin peptides represent another example of a weak MHC-binding ligand that is highly immunogenic, giving rise to distinct populations of autoimmune T cells.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Movement / immunology
  • Coculture Techniques
  • Dose-Response Relationship, Immunologic
  • Epitopes, T-Lymphocyte / metabolism*
  • Histocompatibility Antigens Class II / metabolism*
  • Humans
  • Insulin / immunology*
  • Insulin / metabolism*
  • Islets of Langerhans / immunology
  • Islets of Langerhans / metabolism
  • Islets of Langerhans / pathology
  • Ligands
  • Mice
  • Mice, Inbred NOD
  • Molecular Sequence Data
  • Peptide Fragments / immunology*
  • Peptide Fragments / metabolism*
  • Prediabetic State / immunology*
  • Prediabetic State / metabolism
  • Prediabetic State / pathology
  • Protein Binding / immunology
  • Protein Isoforms / immunology*
  • Protein Isoforms / metabolism*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism*
  • T-Lymphocyte Subsets / pathology

Substances

  • Epitopes, T-Lymphocyte
  • Histocompatibility Antigens Class II
  • I-A g7 antigen
  • Insulin
  • Ligands
  • Peptide Fragments
  • Protein Isoforms
  • insulin B (9-23)