Identification and Characterization of a Tolerogenic T Cell Determinant within Residues 181-209 of Chick Type II Collagen
| Autor: | Andrew H. Kang, Linda K. Myers, Jerome M. Seyer, John M. Stuart, Kuniaki Terato, Steven W. Cooper |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
musculoskeletal diseases
T cell Molecular Sequence Data Immunology Type II collagen Arthritis chemical and pharmacologic phenomena macromolecular substances Biology Epitope Pathology and Forensic Medicine Immune tolerance Arthritis Rheumatoid Epitopes Mice Immune system Immune Tolerance medicine Animals Immunology and Allergy Amino Acid Sequence Amino Acids skin and connective tissue diseases integumentary system Lymphokine T lymphocyte medicine.disease Molecular biology medicine.anatomical_structure Mice Inbred DBA Collagen Peptides Chickens |
| Zdroj: | Clinical Immunology and Immunopathology. 75:33-38 |
| ISSN: | 0090-1229 |
| Popis: | The murine model of collagen-induced arthritis is characterized by the development of an immune response against joint cartilage. Arthritis can be significantly suppressed by the administration of type II collagen (CII) or one of the CNBr peptides, CB11 (CII 124-402) as a tolerogen prior to immunization. We have previously shown that two synthetic peptides, representing sequences CII 260-270 and CII 181209, are effective tolerogens. In this paper, we now characterize the T cell determinant with CII 181-209. A series of synthetic peptides overlapping CII 181-209 and analogs of chick CII 181-209 containing site-directed amino acid substitutions was developed and cultured with T cells from DBA/1 mice immunized with CII. Supernatants were collected and analyzed for the presence of the T cell lymphokine IFN-γ. These data indicate the critical T cell determinant to be located within CII 190-200. This conclusion is further supported by the observation that an unodecapeptide representing CII 190-200 was just as effective as CII 181-209 in suppressing arthritis and anti-CII antibody response when tested as a tolerogen. Analogs containing single amino acid substitutions at residues 191, 194, 197, 198, or 200 were significantly less effective in inducing T cell responses. Each of these peptide analogs was then given as neonatal tolerogens to DBA/1 mice. Mice were subsequently immunized and observed for the development of arthritis. These studies identified residues 194, 197, 198, and 200, and probably residue 191, as critical for tolerance and the suppression of arthritis. Elucidation of the fine structures of T cell determinants which are critical for suppression of arthritis should allow these techniques to be used for developing specific immunotherapeutic approaches to autoimmune arthritis. |
| Databáze: | OpenAIRE |
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