Characterization of a tolerogenic T cell epitope of type II collagen and its relevance to collagen-induced arthritis

Linda Myers, Kuniaki Terato, Jerome M. Seyer, John M. Stuart, Andrew Kang

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

A synthetic peptide representing sequences of type II collagen, (CII 245-270), has previously been used to induce tolerance and suppress arthritis in DBA/1 mice. To determine important residues, a series of peptides, each containing one or two site-directed substitutions, was generated. Mononuclear cells from DBA/1 mice immunized with CII were cultured in the presence of each peptide and the T cell response determined by measuring IFN-γ in culture supernatant fluids. Substitutions within the region CII 260-270 led to significant decreases in IFN-γ responses, identifying this sequence as a T cell epitope. To determine the effects of substitutions within this epitope on arthritis, substituted peptides were administered to neonatal mice as tolerogens. Five site-directed substitutions, four of which included the insertion of a residue found in type I collagen to replace its type II counterpart, abrogated the ability of the peptides to induce tolerance and suppress arthritis. These substitutions were located at residues 260, 261, 263, 264, and 266. Two patterns of T cell reactivity were observed. Peptides containing individual substitutions at positions 261, 264, or 266 were capable of generating a significant T lymphokine response, although those containing substitutions at residues 260 or 263 were ineffective Ag. Systematic analysis of the fine structures of T cell determinants important for autoimmune arthritis can lead to strategies for therapeutic intervention.

Original languageEnglish (US)
Pages (from-to)1439-1443
Number of pages5
JournalJournal of Immunology
Volume149
Issue number4
StatePublished - Aug 15 1992

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T-Lymphocyte Epitopes
Experimental Arthritis
Collagen Type II
Arthritis
Peptides
Inbred DBA Mouse
T-Lymphocytes
Peptide T
Lymphokines
Collagen Type I
Epitopes

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

Characterization of a tolerogenic T cell epitope of type II collagen and its relevance to collagen-induced arthritis. / Myers, Linda; Terato, Kuniaki; Seyer, Jerome M.; Stuart, John M.; Kang, Andrew.

In: Journal of Immunology, Vol. 149, No. 4, 15.08.1992, p. 1439-1443.

Research output: Contribution to journalArticle

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