Tt. Glant et al., CRITICAL ROLES OF GLYCOSAMINOGLYCAN SIDE-CHAINS OF CARTILAGE PROTEOGLYCAN (AGGRECAN) IN ANTIGEN RECOGNITION AND PRESENTATION, The Journal of immunology, 160(8), 1998, pp. 3812-3819
Systemic immunization of BALB/c mice with proteoglycan (aggrecan) from
fetal human cartilage induces progressive polyarthritis, an experimen
tal disease similar to human rheumatoid arthritis, The development of
the disease in this genetically susceptible murine strain is based on
cross-reactive immune responses between the immunizing fetal human and
mouse self-proteoglycans. One of the cross-reactive and arthritogenic
T cell epitopes ((92)GR/QVRVNSA/IY) is localized in the G1 domain of
human/murine proteoglycan, Susceptible BALB/c mice, however, develop a
rthritis only if both the chondroitin sulfate (CS) and keratan sulfate
(KS) side chains of the arthritogenic human proteoglycans are removed
, The function of these tno glycosaminoglycan side chains is opposite,
The presence of a KS side chain in adult proteoglycan inhibits the re
cognition of arthritogenic T cell epitopes, prevents the development o
f T cell response, and protects animals from autoimmune arthritis. In
contrast, the depletion of the CS side chain generates clusters of CS
stubs and provokes a strong B cell response, These carbohydrate-specif
ic B cells are the most important proteoglycan APC. Taken together, pr
oteoglycan-induced progressive polyarthritis is dictated by three majo
r components: genetic background of the BALB/c strain, highly specific
T cell response to epitope(s) masked hy a KS chain in aging tissue, a
nd the presence of proteoglycan (CS stub)-specific B cells required fo
r sufficient Ag presentation.