PERIPHERAL-BLOOD T-LYMPHOCYTES IN SYSTEMIC VASCULITIS - INCREASED T-CELL RECEPTOR V-BETA-2 GENE USAGE IN MICROSCOPIC POLYARTERITIS

Antigen recognition by T lymphocytes is mediated by cell surface recep tors. T cell specificity depends on the variable, diversity and juncti onal (VDJ) regions of the alpha and beta polypeptide chains of the T c ell receptor (TCR). The expression of the variable region genes of the beta chain (V beta) has been analysed to study the involvement of per ipheral blood T cells in systemic vasculitis. RNA was extracted from p eripheral blood lymphocytes of 12 patients with microscopic polyarteri tis, 10 with Wegener's granulomatosis, six with unclassified vasculiti s, and 28 healthy age- and sex-matched individuals. Complementary DNA was made from RNA and amplified by the anchored polymerase chain react ion (PCR) using redundant oligonucleotide primers for the TCR V beta g enes. To determine if the dominant usage of a V beta gene family refle cted the presence of particular T cell clones, cDNA was amplified with primers for the specific V beta gene family. The product was screened for sequence homogeneity by single-stranded conformational polymorphi sm (SSCP) and cloned to sequence the adjoining TCR (D beta)J beta regi on. A significant increase in the mean percentage expression of the V beta 2.1 gene was seen in vasculitis patients (11.4+1.0% (mean+s.e.m.) ) compared with controls (6.6+0.6%; P < 0.003). The most marked increa se was seen in microscopic polyarteritis (13.9+1.7%; P < 0.0001). Ther e were also increases in the expression of V beta 3, 13 and 14 in peri pheral blood of vasculitis patients compared with controls. SSCP analy sis of V beta 2.1 amplified products indicated the presence of oligocl onal bands in a smaller proportion of patients (8/27) than controls (1 2/28). There was no strong evidence for the conservation of the TCR V beta 2.1 junctional region sequence data from a sample group of three patients with oligoclonal bands. Thus, a subset of patients with syste mic vasculitis, particularly those with microscopic polyarteritis, hav e increased TCR V beta 2.1 gene expression in their peripheral blood T cell repertoire. As superantigens binding V beta 2.1 are postulated t o activate T cells with diverse CDR3 sequences, it is proposed that a superantigen is involved in the immunopathogenesis of vasculitis.