Clonally expanded α-chain TCR transcripts are present in skin biopsies of patients with Systemic Sclerosis (135.33)

Abstract

Systemic Sclerosis (SSc) is a chronic autoimmune disease characterized by excessive deposition of collagen in the skin and many internal organs, production of autoantibodies and microvascular alterations. Previous studies in our laboratory have demonstrated the presence of high proportions of identical β-chains TCR transcripts in skin biopsies from patients with SSc of recent onset, suggestive of clonal expansions of T cells. To identify the antigen(s) recognized by clonally expanded T cells in SSc biopsies, we examine the clonality of the α-chain TCR transcripts in patients with SSc. Sequence analysis of α-chain TCR transcripts following non-palindromic PCR/Vα specific PCR and cloning revealed the presence of clonally expanded α-chain TCR transcripts in skin biopsies from four patients with SSc. Substantial proportion of identical α-chain TCR transcripts were found in these skin biopsies accounting from 16% to 32% of the transcripts sequenced. These clonal expansions were confirmed with Vα-specific PCR followed by cloning and sequencing. Identical α-chain TCR transcripts, ranging from 68% to 100%, were identified in individual Vα families. In one of these patients an identical T cell clone was clonally expanded in both peripheral blood and skin. These T cells have undergone clonal expansion in response to, as yet unidentified, specific antigen(s).