Presentation of cartilage proteoglycan to a T cell hybridoma derived from mouse with proteoglycan induced arthritis

F. R. Brennan, G. Negroiu, E. I. Buzas, C. Fulop, K. Hollo, K. Mikecz, T. T. Glant

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Abstract

Immunization of BALB/c mice with human fetal cartilage proteoglycan (PG) produces progressive polyarthritis, and T cells play key roles in the development of the disease. To gain an understanding of how PG is presented to autoreactive T cells by synovial antigen-presenting cells (APC), we examined the abilities of various syngeneic APC in presenting PG to a specific T cell hybridoma 5/4E8, derived from a mouse with PG-induced arthritis. A20 B lymphoma cells and spleen cells were strong presenters of PG, but synoviocytes and P388D1 macrophages could only present PG effectively after stimulation with interferon-gamma (IFN-γ). The IFN-γ exerted its effect by upregulating both MHC class II and intercellular adhesion molecule-1 (ICAM-1) expression by these cells as neutralizing antibodies to Ia, LFA-1 and ICAM-1 inhibited presentation. Our studies also showed that synoviocytes and spleen cells took up and processed PG more rapidly than the cell lines. Cysteine and serine protease-dependent antigen presentation of PG was blocked at 4°C, 18°C and by chloroquine treatment, indicating that presentation required active uptake and processing in an acidic compartment, probably in lysosomes. Also, keratan sulphate-depleted and cyanogen bromide (CNBr) and 2-nitro-5-thiocyanobenzoic acid (NTCB)-cleaved PG elicited stronger T cell responses, as they were more easily processed than the native molecule. Furthermore, CNBr-generated peptides were presented by fixed APC, indicating that core protein fragments of cartilage PG can be presented directly by APC in context with MHC class II molecules.

Original languageEnglish
Pages (from-to)104-110
Number of pages7
JournalClinical and Experimental Immunology
Volume100
Issue number1
Publication statusPublished - Jan 1 1995

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Keywords

  • Antigen presentation
  • Arthritis animal model
  • Proteoglycan
  • T hybridoma

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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