Human cartilage aggrecan CS1 region contains cryptic T-cell recognition sites.
Cartilage proteoglycan aggregates (PG) are candidate T-cell autoantigens in the pathogenesis of rheumatoid arthritis (RA). We have investigated the possibility that responses to class II-restricted T-cell recognition sites in human cartilage aggrecan (core protein) may depend upon whether these sites are available as free peptide antigens or as part of intact monomers. Analysis of mouse T-cell responses to intact or deglycosylated monomers, purified from human articular cartilage, and to synthetic peptides of the chondroitin sulphate (CS) attachment region homologous repeat sequence showed that recognition of T-cell epitopes in the CS1 region was strongly dependent upon the form of antigen used. The results show that the CS1 region contains cryptic T-cell recognition sites and raise the possibility that fragments of PG, released through the action of extracellular proteases in inflamed joints, may be capable of activating T cells with specificities for epitopes which are not made available following processing of intact PG. T cells with specificities for cryptic epitopes in PG may play a role in the pathogenesis of RA.
Department of Medicine, Rheumatology, Medical School, University of Newcastle upon Tyne, U.K.
J A
JA
Goodacre
S
S
Middleton
S
S
Lynn
D A
DA
Ross
J
J
Pearson
D053674:Aggrecans; D000595:Amino Acid Sequence; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D002358:Cartilage, Articular / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D002460:Cell Line; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D008698:Mesylates / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology; D011509:Proteoglycans / Q000737:chemistry / Q000187:drug effects / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
C508320:Acan protein, mouse; D053674:Aggrecans; D001324:Autoantigens; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D008698:Mesylates; D010455:Peptides; D011509:Proteoglycans; C012077:trifluoromethanesulfonic acid