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T cell epitopes of type II collagen that regulate murine collagen-induced arthritis.

Abstract
Chick type II collagen (CII), a protein commonly found in joint cartilage, induces an autoimmune arthritis when administered to susceptible strains of mice. A cyanogen bromide fragment of CII, CB11, contains the requisite epitopes critical for inducing collagen-induced arthritis. If administered as a tolerogen, however, before immunization, CB11 prevents the onset of disease. Therefore, delineation of structural elements of CB11 that can regulate autoreactive T cells became the goal of this study. To delineate the structural elements of CB11 antigenic to T cells, 14 peptides containing overlapping sequences of CB11 were generated. Mononuclear cells from CII-immunized DBA/1 mice were cultured with these peptides and the resulting supernatants examined for the production of IFN-gamma. Two peptides, CII 181-209 and CII 245-270, generated the greatest responses. The ability of these two peptides to regulate arthritis was tested by administering them to neonatal DBA/1 mice as tolerogens before immunization with CII. Both peptides suppressed the incidence of arthritis whereas no other peptide used as a tolerogen significantly altered the course of the disease. T cells from four arthritis-resistant murine strains did not recognize either peptide when immunized with CII, whereas cells from the disease-susceptible B10.Q mice responded well to both. Thus, the coincidence of T cell responses to CII 181-209 and CII 245-270 in CIA-susceptible mice and the lack of response in disease-resistant strains or CII-tolerized mice identify these two peptides as containing important T cell epitopes that regulate CIA.
AuthorsL K Myers, J M Seyer, J M Stuart, K Terato, C S David, A H Kang
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 151 Issue 1 Pg. 500-5 (Jul 01 1993) ISSN: 0022-1767 [Print] United States
PMID7686947 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Autoantigens
  • Epitopes
  • Collagen
Topics
  • Amino Acid Sequence
  • Animals
  • Animals, Newborn (immunology)
  • Arthritis (immunology)
  • Autoantigens (chemistry, immunology)
  • Autoimmune Diseases (immunology)
  • Collagen (immunology)
  • Epitopes
  • Immune Tolerance
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred Strains
  • Molecular Sequence Data
  • T-Lymphocytes (immunology)

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