Blood, Vol. 92 No. 10 (November 15), 1998:
pp. 3737-3744
T-Cell Expansions With Conserved T-Cell Receptor 
Chain Motifs
in the Peripheral Blood of HLA-DRB1*0401 Positive Patients With
Necrotizing Vasculitis
Johan Grunewald,
Eva Halapi,
Jan Wahlström,
Ricardo Giscombe,
Soniya Nityanand,
Carani Sanjeevi, and
Ann-Kari Lefvert
From the Microbiology and Tumorbiology Center (MTC), Karolinska
Institute, Stockholm; and the Immunological Research Laboratory,
Department of Medicine and the Department of Molecular Medicine,
Karolinska Hospital, Stockholm, Sweden.
T lymphocytes are implicated in the pathogenesis of systemic
vasculitis such as Wegener's granulomatosis (WG) and polyarteritis nodosa (PAN). In the present study, we have characterized in detail the
T-cell receptor (TCR) of peripheral blood T cells from eight vasculitis
patients of known HLA class II genotypes. We used flow cytometry to outline the exact TCR V gene expression, complementarity determining region 3 (CDR3) fragment analysis to estimate the degree of
clonality and cDNA sequencing to define the exact TCR 
or 
chain
sequences. The TCR CDR3 region interacts with antigenic peptides
presented by HLA molecules, and it is normally immensely diverse. It
was therefore of particular interest to identify a common dominating
TCR BV8-F/L-G-G-A/Q-G-J2S3 chain sequence in the CD4+
T cells of four unrelated vasculitis patients. Furthermore, this BV8-associated CDR3 motif was linked to the HLA-DRB1*0401 allele, as
well as to active disease and/or an established
BV8+ CD4+ T-cell expansion. In contrast,
age- and HLA-matched patients with rheumatoid arthritis did not harbor
the described BV8 motif. These results strongly suggest that
BV8+ CD4+ T cells with the described CDR3
motif recognize a specific antigen presented by DR4 molecules,
indicating the existence of a common vasculitis-associated antigen.
