Mapping of arthritogenic/autoimmune epitopes of cartilage aggrecans in proteoglycan-induced arthritis.
Immunization of BALB/c mice with chondroitin sulfate-depleted proteoglycan (aggrecan) of fetal human cartilage produces progressive polyarthritis and ankylosing spondylitis. The development of the disease in genetically susceptible BALB/c mice is dependent upon the expression of both cell-mediated and humoral immune responses against the host mouse cartilage proteoglycan (PG). Although cartilage PGs from various species have many biochemical and immunological similarities, only a select group of PGs from fetal and newborn human, fetal pig and canine articular cartilages, human osteophytes and human chondrosarcomas are able to induce arthritis in BALB/c mice. Arthritis develops only in mice that also develop autoantibodies to self-cartilage PGs, although autoantibodies occasionally are present in non-arthritic animals as well. The protease-sensitive auto/arthritogenic epitope(s) is located in, or close to, the chondroitin sulfate (CS) attachment region of the PG molecule. The primary structure of the core protein is responsible for the autoimmune/arthritogenic effect of this select group of PGs, whereas the core protein epitopes are masked by glycosaminoglycan (GAG)-side chains. The CS side chains seem to inhibit antigen recognition in all aggrecans with arthritogenic potential, whereas a similar effect with keratan sulfate (KS) appears only in PGs of aging cartilages.
Glant
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TT
Department of Biochemistry, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, USA.
Fülöp
C
C
Cs-Szabó
G
G
Buzás
E
E
Ragasa
D
D
Mikecz
K
K
D053674:Aggrecans; D000818:Animals; D001168:Arthritis / Q000276:immunology*; D015551:Autoimmunity; D002358:Cartilage, Articular / Q000378:metabolism*; D002417:Cattle; D000939:Epitopes; D016326:Extracellular Matrix Proteins; D005260:Female; D006801:Humans; D007120:Immunochemistry; D037181:Lectins, C-Type; D051379:Mice; D008807:Mice, Inbred BALB C; D011509:Proteoglycans / Q000737:chemistry / Q000276:immunology*
C508320:Acan protein, mouse; D053674:Aggrecans; D000939:Epitopes; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D011509:Proteoglycans