Use of Soluble Peptide-DR4 Tetramers to Detect Synovial T Cells Specific for Cartilage Antigens in Patients with Rheumatoid Arthritis

Considerable evidence indicates that CD4+T cells are important in the pathogenesis of rheumatoid arthritis (RA), but the antigens recognized by these T cells in the joints of patients remain unclear. Previous studies have suggested that type II collagen (CII) and human cartilage gp39 (HCgp39) are among the most likely synovial antigens to be involved in T cell stimulation in RA. Furthermore, experiments have defined dominant peptide determinants of these antigens when presented by HLA-DR4, the most important RA-associated HLA type. We used fluorescent, soluble peptide-DR4 complexes (tetramers) to detect synovial CD4+T cells reactive with CII and HCgp39 in DR4+patients. The CII-DR4 complex bound in a specific manner to CII peptide-reactive T cell hybridomas, but did not stain a detectable fraction of synovial CD4+cells. A background percentage of positive cells (