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

• Published in: Cellular Immunology 2005-06, Vol.235 (2), p.98-108
• Main Authors: Buzás, Edit I., Végvári, Anikó, Murad, Yanal M., Finnegan, Alison, Mikecz, Katalin, Glant, Tibor T.
• Format: Article
• Language: English
• Subjects: Aggrecans; Amino Acid Sequence; Animals; Arthritis; Arthritis - immunology; B-Lymphocytes - immunology; Cartilage - chemistry; Cartilage - immunology; Cell Proliferation; Cells, Cultured; Conditionally immunogenic; Cryptic epitopes; Cytokines - secretion; Epitopes - chemistry; Epitopes - immunology; Extracellular Matrix Proteins - chemistry; Extracellular Matrix Proteins - immunology; Full activator; Humans; Lectins, C-Type - chemistry; Lectins, C-Type - immunology; Mice; Molecular Sequence Data; Partial activation; Peptide Fragments - pharmacology; Proteoglycan-induced arthritis; Proteoglycans - chemistry; Proteoglycans - immunology; Sequence Homology, Amino Acid; T-cell epitopes; T-cell responses; T-Lymphocytes - chemistry; T-Lymphocytes - cytology; T-Lymphocytes - immunology; T-Lymphocytes - secretion
• ISSN: 0008-8749; 1090-2163; 1365-2567
• DOI: 10.1016/j.cellimm.2004.08.006

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.”