T-CELL EXPANSIONS WITH CONSERVED T-CELL RECEPTOR-BETA CHAIN MOTIFS INTHE PERIPHERAL-BLOOD OF HLA-DRB1-ASTERISK-0401 POSITIVE PATIENTS WITHNECROTIZING VASCULITIS

T lymphocytes are implicated in the pathogenesis of systemic vasculiti s such as Wegener's granulomatosis (WG) and polyarteritis nodosa (PAN) , In the present study, we have characterized in detail the T-cell rec eptor (TCR) of peripheral blood T cells from eight vasculitis patients of known HLA class II genotypes. We used flow cytometry to outline th e exact TCR V gene expression, complementarity determining region 3 (C DR3) fragment analysis to estimate the degree of clonality and cDNA se quencing to define the exact TCR alpha or beta chain sequences. The TC R CDR3 region interacts with antigenic peptides presented by HLA molec ules, and it is normally immensely diverse. it was therefore of partic ular interest to identify a common dominating Top BV8-F/L-G-G-A/Q-G-J2 S3 beta chain sequence in the CD4(+) T cells of four unrelated vasculi tis patients. Furthermore, this BV8-associated CDR3 motif was linked t o the HLA-DRB10401 allele, as well as to active disease and/or an est ablished BV8(+) CD4(+) T-cell expansion. In contrast, age- and HLA-mat ched patients with rheumatoid arthritis did not harbor the described B V8 motif. These results strongly suggest that BV8(+) CD4(+) T cells wi th the described CDR3 motif recognize a specific antigen presented by DR4 molecules, indicating the existence of a common vasculitis-associa ted antigen. (C) 1998 by The American Society of Hematology.