Abstract
Susceptibility to collagen induced arthritis (CIA) in the murine model is linked to expression of the MHC class II alleles, I-Aq and I-Ar. We have examined the molecular basis for this MHC-linked susceptibility by studying the antigen presentation function of two class II molecules, I-Aq and I-Ap, that are closely related yet differ in mediating susceptibility to CIA. These class II molecules differ by only 4 amino acids, yet only mice expressing I-Aq develop CIA. Although the I-Ap molecule can bind the same immunodominant determinant from type II collagen as I-Aq, H-2p APC have difficulty generating I-Ap:CII peptide complexes when processing of CII is required. Immunization of H-2p mice with type II collagen (CII) generated only a weak T cell response when compared to H-2q mice, whereas immunization with the a CII peptide containing the dominant determinant induced a strong T cell response in both strains. In antigen presentation assays, H-2p APC were very inefficient in stimulating T cells when native CII was used as antigen, however they presented CII synthetic peptides with similar efficiency as H-2q APC. Processing and presentation of other antigens by H-2p APC was not affected. Using soluble class II binding assays, the a...Continue Reading
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