T-cell recognition of differentially tolerated epitopes of cartilage proteoglycan aggrecan in arthritis.
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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Section 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.
Végvári
Anikó
A
Murad
Yanal M
YM
Finnegan
Alison
A
Mikecz
Katalin
K
Glant
Tibor T
TT
D053674:Aggrecans; D000595:Amino Acid Sequence; D000818:Animals; D001168:Arthritis / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D002356:Cartilage / Q000737:chemistry / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D037181:Lectins, C-Type / Q000737:chemistry / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology; D011509:Proteoglycans / Q000737:chemistry / Q000276:immunology*; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000737:chemistry / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
C508320:Acan protein, mouse; D053674:Aggrecans; D016207:Cytokines; D000939:Epitopes; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D010446:Peptide Fragments; D011509:Proteoglycans