Induction of arthritis in SCID mice by T cells specific for the “shared epitope” sequence in the G3 domain of human cartilage proteoglycan

Abstract

Peptide p135H, corresponding to the peptide sequence in the G3 domain of human cartilage proteoglycan aggrecan, is immunogenic/arthritogenic in BALB/c mice. Peptide p135H includes a highly homologous motif of the shared epitope, a sequence that is overrepresented in bacterial heat-shock proteins, envelope protein of human JC polyomavirus, and numerous HLA-DR4 alleles. Since the G3 domain of cartilage proteoglycan aggrecan with the p135 sequence is "lost" during the normal metabolic turnover of cartilage proteoglycan or in pathologic conditions, an antigenoriented T cell migration into joints of presensitized (susceptible) individuals may contribute to the organ-specificity of RA.