Molecular manipulation with the arthritogenic epitopes of the G1 domain of human cartilage proteoglycan aggrecan

Y. M. Murad, Z. Szabó, K. Ludányi, Tibor T. Glant

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Systemic immunization of BALB/c mice with human cartilage proteoglycan (PG) aggrecan induces progressive polyarthritis. The G1 domain of the PG aggrecan molecule contains most of the T cell epitopes, including three immunodominant ('arthritogenic') and at least six subdominant T cell epitopes. The three dominant T cell epitopes (P49, P70 and P155) were deleted individually or in combination by site directed mutagenesis, and the recombinant human G1 (rhG1) domain (wild type and mutated) proteins were used for immunization. Close to 100% of BALB/c mice immunized with the wild-type (nonmutated) rhG1 domain developed severe arthritis, which was 75% in the absence of P70 (5/4E8) epitope, and very low (<10% incidence) when all three dominant T cell epitopes were deleted. The onset was delayed and the severity of arthritis reduced in animals when dominant T cell epitopes were missing from the immunizing rhG1 domain. The lack of T cell response to the deleted epitope(s) was specific, but the overall immune response against the wild-type rhG1 domain of human PG was not significantly affected. This study helped us to understand the dynamics and immune-regulatory mechanisms of arthritis, and supported the hypothesis that the development of autoimmune arthritis requires a concerted T cell response to multiple epitopes, rather than the immune response to a single arthritogenic structure.

Original languageEnglish
Pages (from-to)303-311
Number of pages9
JournalClinical and Experimental Immunology
Volume142
Issue number2
DOIs
Publication statusPublished - Nov 2005

Fingerprint

Aggrecans
Proteoglycans
T-Lymphocyte Epitopes
Cartilage
Epitopes
Arthritis
Immunization
T-Lymphocytes
Site-Directed Mutagenesis
Incidence
Proteins

Keywords

  • Aggrecan
  • Animal model
  • Arthritis
  • Rheumatoid arthritis
  • T cell epitopes

ASJC Scopus subject areas

  • Immunology

Cite this

Molecular manipulation with the arthritogenic epitopes of the G1 domain of human cartilage proteoglycan aggrecan. / Murad, Y. M.; Szabó, Z.; Ludányi, K.; Glant, Tibor T.

In: Clinical and Experimental Immunology, Vol. 142, No. 2, 11.2005, p. 303-311.

Research output: Contribution to journalArticle

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