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

Clin Exp Immunol. 1995 Apr;100(1):104-10. doi: 10.1111/j.1365-2249.1995.tb03610.x.

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-gamma). The IFN-gamma exerted its effect by up-regulating 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 degrees C, 18 degrees 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.

Publication types

  • 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.

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology*
  • Arthritis / immunology*
  • Biological Transport
  • Cartilage / immunology*
  • Chloroquine / pharmacology
  • Hybridomas / immunology
  • Intercellular Adhesion Molecule-1 / metabolism
  • Interleukin-2 / biosynthesis
  • Lymphocyte Function-Associated Antigen-1 / immunology
  • Mice
  • Mice, Inbred BALB C
  • Protease Inhibitors / pharmacology
  • Proteoglycans / chemistry
  • Proteoglycans / immunology*
  • Proteoglycans / metabolism
  • Spleen / cytology
  • Spleen / immunology
  • Structure-Activity Relationship
  • T-Lymphocytes / immunology*
  • Temperature

Substances

  • Interleukin-2
  • Lymphocyte Function-Associated Antigen-1
  • Protease Inhibitors
  • Proteoglycans
  • Intercellular Adhesion Molecule-1
  • Chloroquine