In order to develop an ultimate therapy to overcome autoimmune diseases, it is very important to identify whether or not autoantigen-reactive T cells accumulate in such diseases. A novel method was established to analyze T cell clonality using a combination of reverse transcriptase-polymerase chain reaction of T cell receptor beta chain transcripts and single-strand conformation polymorphism (RT-PCR/SSCP). Using RT-PCR/SSCP, clonal expansion of T cells were identified in NOD mouse, collagen induced arthritis model, rheumatoid arthritis, Crohn's disease, Sjögren's syndrome, bone marrow transplantation, pregnancy, malignant tumors, HTLV-I associated myopathy, and interstitial pneumonia. By using a tandem mass spectrometry or a lymphocytic proliferation assay, T cell epitopes were mapped in NOD mice, EAE, MCTD, and melanoma.