Altered peptide ligands control type II collagen-reactive T cells from rheumatoid arthritis patients

Mod Rheumatol. 2006;16(4):226-8. doi: 10.1007/s10165-006-0495-1.

Abstract

We previously reported that peripheral blood mononuclear cells from HLA-DRB1*0101 Japanese patients with rheumatoid arthritis (RA) were highly reactive to 256-271 peptide of type II collagen (CII). In this report, we tried to regulate the CII reactivity of T cells from RA patients with HLA-DRB1*0101 by altered peptide ligand (APL), which is a single amino acid substitution of the T-cell epitope on CII 256-271 peptide. Antagonistic activity of 21 APLs was assessed using three different T-cell lines. Results showed that 262 (G-->A) APL of CII 256-271 exhibited antagonistic activity in all T-cell lines and it was suggested that the application of CII APL might be a new therapeutic strategy in the regulation of RA.

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / metabolism
  • Arthritis, Rheumatoid / therapy*
  • Cell Division / immunology
  • Cell Line
  • Collagen Type II / genetics
  • Collagen Type II / metabolism
  • Collagen Type II / pharmacology*
  • HLA-A Antigens / genetics
  • HLA-DRB1 Chains
  • Humans
  • In Vitro Techniques
  • Ligands
  • Lymphocyte Activation / immunology
  • Molecular Sequence Data
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology*
  • Receptors, Antigen, T-Cell / antagonists & inhibitors
  • Receptors, Antigen, T-Cell / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / metabolism

Substances

  • Collagen Type II
  • HLA-A Antigens
  • HLA-DRB1 Chains
  • HLA-DRB1*01:01 antigen
  • Ligands
  • Peptide Fragments
  • Receptors, Antigen, T-Cell