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* Division of Immunology, Beckman Research Institute, City of Hope Medical Center, Duarte, CA 91010;
Division of Rheumatology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033; and
Bone and Cartilage Research Laboratory, A. I. DuPont Hospital for Children, Wilmington, DE 19899
Rheumatoid arthritis is characterized by synovial joint
infiltration of activated CD4+ T cells and MHC class
II+ APC, and is linked to specific HLA-DR alleles.
Candidate autoantigens in synovial fluid and cartilage include type II
collagen (CII) and cartilage gp39 (HCgp39). Using preparations of
native Ag and T cells derived from Ag-immunized DR4-transgenic mice, we
determined that human ex vivo differentiated DR4+ dendritic
cells (DC) and macrophages (M
) can mediate MHC class II presentation
of CII or HCgp39 epitopes. The form of the Ag (soluble, partially
degraded, or particulate) delivered to the APC influenced its
presentation by DC and M. DC efficiently presented partially
degraded, but not native CII 
-chains, while M presentation was
most efficient after phagocytosis of bead-conjugated CII. Both DC and
M presented soluble HCgp39, and activated M from some donors
presented epitopes derived from endogenously synthesized HCgp39. When
synovial fluid from rheumatoid arthritis patients was used as a source
of Ag, DC presentation of HCgp39 and CII epitopes was efficient,
indicating that synovial fluid contains soluble forms of CII and HCgp39
amenable to internalization, processing, and presentation. These data
support the hypothesis that CII and HCgp39 are autoantigens and
that their class II-mediated presentation by DC and M to T cells in
vivo has a critical role in the pathogenesis of human rheumatoid
arthritis.
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