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Cell Immunol. 2005 Jun;235(2):98-108. Epub 2005 Sep 23.

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

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  • 1Section of Biochemistry and Molecular Biology, Department of Orthopedic Surgery, Biochemistry, Immunology/Microbiology, and Internal Medicine (Section of Rheumatology), Rush University Medical Center, Chicago, IL 60612, USA.

Abstract

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."

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