T Cell Receptor (Tcr) Repertoire in Coeliac Disease (Cd): Conserved Junctional Sequences in the Untreated Mucosa.

In untreated coeliac disease (CD) the lesion of the jejunal mucosa is characterized by an extensive infiltration of ?? T cells. In order to characterize T cells at the site of the lesion we have investigated their V? usage, and we have already shown, by an immunohistochemical approach, that cells expressing V?8 are significantly more represented in the lamina propria of untreated coeliac patients than in that of controls (1). The observed increase in the V?8 subset was too small to be attributed to a superantigen effect; nevertheless, it could reflect selection of specific T cell clones by an antigen involved in the pathogenesis of the disease. TCR diversity in the V?8 subset was then examined.We analysed V?8 transcripts from jejunal biopsies from 7 untreated coeliacs (median age 5 years, range 1.5-13.7) and from 5 controls (median age 2.7 years, range 1.1-9.5). The V?8 segment was amplified using a V?8 specific primer by RT-PCR, the PCR product was cloned in E Coli and subsequently sequenced.Identical CDR3 regions were found in different patients. One of these was present in 3/7 and other two in 2/7 coeliacs. In no case these shared CDR3 sequences were found in the controls, nor in the peripheral blood of patients expressing them in the jejunum.The present data suggest that expanded clones are present in the untreated coeliac mucosa. Such local expansion, not detected in the periphery, suggests a possible role in the pathogenesis of the disease. The isolation of T cell clones bearing these CDR3 sequences could represent an useful tool for the identification of antigenic epitopes involved in CD.