부산대학교 도서관

Coeliac disease has a known strong linkage with the HLA complex and has also recently been linked to the T cell receptor genes but the mechanism whereby these genes confer susceptibility is not known. This study has examined two possible mechanisms: (i) direct, lectin-like binding of α-gliadin (the causative agent of CD) to HLA or TcR molecules and (ii) antigenic cross-reactivity between α-gliadin and HLA or TcR molecules, A flow cytometer was used to assess interactions between α-gliadin, anti-α-gliadin antibodies (raised in both coeliac patients and in rabbits) and EBV-transformed B cell lines from coeliac patients and HLA-matched and mismatched normal controls. The B cell lines were shown lo express HLA-DP, -DQ and -DR antigens which are also found on coeliac intestinal epithelial cells. After incubating B cell lines with α-gliadin over a wide range of concentrations, no binding of α-gliadin to any of the cell lines could be detected with either of the gliadin-specific antibodies. This suggests that HLA molecules do not bind to α-gliadin in a lectin-like fashion. In contrast to the B cell lines, α-gliadin binding lo peripheral blood monocytes could be demonstrated. This binding occurred equally to patient and control monocytes and was not influenced by HLA allotype. The second possibility tested was that α-gliadin and the disease-associated HLA molecule bear antigenic similarities. However, neither rabbit anti-gliadin serum nor purified human α-gliadin antibody bound directly to the B cell lines. Using peripheral blood T cells similar results were obtained; no binding of α-gliadin or antibodies to α-gliadin was found. Thus this study shows that the HLA and TcR associations with CD are not explained by the direct binding of α-gliadin to these molecules nor by a sharing of antigenic determinants between α-gliadin and these molecules. [ABSTRACT FROM AUTHOR]