It has been proposed that
peptide epitopes bind to
MHC class II molecules to form distinct structural conformers of the same
MHC II-peptide complex termed type A and type B, and that the two conformers of the same
peptide-MHC II complex are recognized by distinct CD4 T cells, termed type A and type B T cells. Both types recognize short synthetic
peptides but only type A recognize endosomally processed intact
antigen. Type B T cells that recognize self
peptides from exogenously degraded
proteins have been shown to escape negative selection during thymic development and so have the potential to contribute to the pathogenesis of autoimmunity. We generated and characterized mouse CD4 T cells specific for an arthritogenic
epitope of the candidate joint
autoantigen proteoglycan aggrecan. Cloned T-cell hybridomas specific for a synthetic
peptide containing the
aggrecan epitope showed two distinct response patterns based on whether they could recognize processed intact
aggrecan. Fine mapping demonstrated that both types of T-cell recognized the same core
epitope. The results are consistent with the generation of
aggrecan-specific type A and type B T cells. Type B T cells were activated by supernatants released from degrading cartilage, indicating the presence of antigenic extracellular
peptides or fragments of
aggrecan. Type B T cells could play a role in the pathogenesis of
proteoglycan-induced
arthritis in mice, a model for
rheumatoid arthritis, by recognizing extracellular
peptides or
protein fragments of joint
autoantigens released by inflamed cartilage.