Altered collagen II peptides inhibited T-cell activation in rheumatoid arthritis

Clin Immunol. 2006 Feb-Mar;118(2-3):317-23. doi: 10.1016/j.clim.2005.09.020. Epub 2005 Dec 15.

Abstract

It has been reported that collagen II (CII)-derived peptide induced T-cell activation via its amino acids responsible for T-cell receptor (TCR) recognition. In this study, three altered CII263-272 peptide ligands (APL) containing multiple substitutions of TCR contact residues were synthesized. Their roles in inhibition of T-cell activation were evaluated in peripheral blood lymphocytes (PBL) of rheumatoid arthritis (RA) in vitro. It was shown that 41% (25/61) of RA patients were responsive to the wild-type antigenic CII263-272. In contrast, marginal or silent T-cell responses to the three APLs were found, accompanied by inhibitory effects on secretion of Th1 type cytokines and expression of cell surface markers, CD69 and CD25. In addition, T-cell activation induced by the wild-type antigenic CII263-272 was inhibited by all the three APLs in a dose-dependent manner. It is demonstrated that APLs with substitutions of TCR contact residues are capable of down-regulating T-cell responses in PBLs of RA, suggesting that the CII-derived APLs are potentially therapeutic in RA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / biosynthesis
  • Antigens, CD / genetics
  • Antigens, Differentiation, T-Lymphocyte / biosynthesis
  • Antigens, Differentiation, T-Lymphocyte / genetics
  • Arthritis, Rheumatoid / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Proliferation
  • Cells, Cultured
  • Collagen Type II / immunology*
  • Collagen Type II / metabolism
  • Cytokines / metabolism
  • Female
  • HLA-DR4 Antigen / immunology
  • HLA-DR4 Antigen / metabolism
  • Humans
  • Immunosuppressive Agents / pharmacology*
  • Lectins, C-Type
  • Ligands
  • Lymphocyte Activation / immunology*
  • Male
  • Middle Aged
  • Peptide Fragments / immunology*
  • Peptide Fragments / metabolism
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Interleukin-2 / biosynthesis
  • Receptors, Interleukin-2 / genetics
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD69 antigen
  • Collagen Type II
  • Cytokines
  • HLA-DR4 Antigen
  • Immunosuppressive Agents
  • Lectins, C-Type
  • Ligands
  • Peptide Fragments
  • Receptors, Antigen, T-Cell
  • Receptors, Interleukin-2