T-cell recognition of differentially tolerated epitopes of cartilage proteoglycan aggrecan in arthritis

Cell Immunol. 2005 Jun;235(2):98-108. doi: 10.1016/j.cellimm.2004.08.006. Epub 2005 Sep 23.


Proteoglycan (PG) aggrecan, a major macromolecular component of cartilage, is highly immunogenic; it induces arthritis in genetically susceptible BALB/c mice. The present study maps the T-cell epitope repertoire of cartilage PG by identifying a total of 27 distinct T-cell epitopes. An epitope hierarchy, accounting for the different effector functions of PG-specific T cells, and determinant spreading, has been found. T-cell responses to four epitopes were associated with arthritis induction. Some of the T-cell epitopes were full T-cell activators, whereas a number of subdominant and cryptic epitopes proved to be partial activators in vitro, inducing either cytokine secretion or T-cell proliferation, but not both. A few T-cell epitopes of the core protein of cartilage PG were clearly recognized by T cells in PG-immunized arthritic animals, but the corresponding peptides did not induce T-cell responses when injected into naive BALB/c mice; thus these T-cell epitopes were designated as "conditionally immunogenic."

MeSH terms

  • Aggrecans
  • Amino Acid Sequence
  • Animals
  • Arthritis / immunology*
  • B-Lymphocytes / immunology
  • Cartilage / chemistry
  • Cartilage / immunology*
  • Cell Proliferation
  • Cells, Cultured
  • Cytokines / metabolism
  • Epitopes / chemistry
  • Epitopes / immunology*
  • Extracellular Matrix Proteins / chemistry
  • Extracellular Matrix Proteins / immunology*
  • Humans
  • Lectins, C-Type / chemistry
  • Lectins, C-Type / immunology*
  • Mice
  • Molecular Sequence Data
  • Peptide Fragments / pharmacology
  • Proteoglycans / chemistry
  • Proteoglycans / immunology*
  • Sequence Homology, Amino Acid
  • T-Lymphocytes / chemistry
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism


  • Acan protein, mouse
  • Aggrecans
  • Cytokines
  • Epitopes
  • Extracellular Matrix Proteins
  • Lectins, C-Type
  • Peptide Fragments
  • Proteoglycans