Dominant and shared T cell receptor beta chain variable regions of T cellsinducing synovial hyperplasia in rheumatoid arthritis

Previously, we demonstrated the presence of at least two distinct subpopula tions of patients with rheumatoid arthritis (RA) employing a cell-transfer experiment using severe combined immunodeficient (SCID) mice. One group of patients, whose T cells derived from the rheumatoid joints, induced synovia l hyperplasia (SB) in the SCID mice (the positive group) The other group di d not display the induction of SH (the negative group). TCR/V beta gene usa ge-analysis indicated that some dominant T cell subpopulations were oligocl onally expanding only in the rheumatoid joints, and not in the periphery of the patients of the positive group. Moreover, these T cell subpopulations were not seen in the joints of patients in the negative group or in non-RA patients. In addition, the preferential uses of certain TCR/V beta s (V bet a 8, V beta 12, V beta 13, and V beta 14) genes were demonstrated in these T cells. In this study, to investigate whether these T cells are driven by a certain antigen(s), the third complementarity determining regions (CDR3s) of TCR/V beta, especially V beta 8 and V beta 14 PCR products, were cloned and sequenced. As a result, a dominant CDR3 sequence, CASS-PRERAT-YEQ, was found in V beta 14+ T cells from the rheumatoid joint of a patient (Patien t 1) of the positive group with a V beta 14 skew. The identical CDR3 sequen ce also predominated in V beta 14+ T cells from the rheumatoid joint of ano ther patient (Patient 7) of the positive group with a V beta 14 skew. In ad dition, in the patients (Patients 4, 7, 8) of the positive group with a V b eta 8 skew, other dominant CDR3 sequences, CASS-ENS-YEQ and CASS-LTEP-DTQ, were found as in the case of V beta 14. However, no identical CDR3 sequence s were detected dominantly in the joints of the patients in the negative gr oup or in non-RA patients. A V beta 14+ T cell clone (TCL), named G3, with the identical CDR3 sequence, CASS-PRERAT-YEQ, was isolated successfully fro m Patient 1, and cell transfer of G3 with autologous irradiated peripheral mononuclear cells induced SH in the SCID mice. Taken together, these result s suggest that T cells inducing SH, thought to be pathogenic for RA might b e driven by a certain shared antigen(s). (C) 1999 Academic Press.