A method to determine antigen peptides for the conally expanded T cells in systemic autoimmune diseases

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We previously reported oligoclonal T cell accumulation in the systemic autoimmune diseases. For instance, the T cell clonal expansion was detected in peripheral blood and also in affected kidney in systemic lupus erythematosus (SLE) and in synovial tissue in rheumatoid arthritis (RA). However, target molecules of these accumulated or expanded T cells remains to be determined, even though they are of great importance for understanding the pathogenesis of the diseases. To determine the antigen-peptides of the T cell clonotypes, we tried to establish screening system of antigenic peptides using random peptide phage library with MHC molecules and reconstructed TCR from clinical samples. As a result, we demonstrated that HLAB5101 and H-2Db with betamicroglobulin is expressed on phage with ability to bind antigenic peptides. Further, we obtained TCR a and b chain in pair from one T cell of clinical samples from patients with SLE, using single cell PCR and reconstructed the TCR as a single chain in vitro. Combination of the reconstructed TCR and randomized peptide library would be a powerful tool to determine the antigens for the clonally expanded T cells.