Generation of transgenic animals expressing the α and β chains of the autoreactive T-cell receptor

Abstract

Transgenic animal analysis has become a key approach used to study the gene functions and to model various human diseases, including autoimmune disorders. Such disorders are caused by the activation of T-cell clones whose T-cell receptors (TCRs) have a high affinity for syngeneic MHC molecules. The genes coding for the α and β chains of the autoreactive TCR were cloned from hybridoma 7, which was specific for syngeneic Ab MHC class II molecules. Amplified DNA fragments containing rearranged genomic DNA of the α and β chains of hybridoma 7 were cloned into special cassette vectors that contained the natural promoter and enhancer elements ensuring direct expression of the α- and β-chain genes in T cells of transgenic animals. The animals obtained with the vectors expressed the α or β chain on the majority of peripheral Tcells. The animals are suitable for studying the features of the intrathymic selection and maturation of T cells and provide an experimental model for developing new approaches to therapy of autoimmune diseases.