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Gamma-aminobutyric acid (GABA) is synthesized by two isoforms of the pyridoxal 5'-phosphate-dependent enzyme glutamic acid decarboxylase (GAD65 and GAD67). GAD67 is constitutively active and is responsible for basal GABA production. In contrast, GAD65, an autoantigen in type I diabetes, is transiently activated in response to the demand for extra GABA in(More)
Organ specific autoimmune diseases are relatively common immunological disorders in man which include thyroid autoimmune disease, insulin-dependent diabetes mellitus and myasthenia gravis. The target autoantigens in some of these diseases have recently been characterised. In thyroid autoimmune disease this includes the key enzyme, thyroid peroxidase (TPO),(More)
Autoantibodies to the diabetes autoantigen, the 65kDa isoform of glutamic acid decarboxylase (GAD65), react with conformational epitopes defined according to linear sequences but not according to structural information, or contact sites with the antibody paratope. To ascertain such information for an exemplary human monoclonal antibody (mAb) to GAD65, b78,(More)
Thyroid peroxidase (TPO) catalyses the biosynthesis of thyroid hormones and is a major autoantigen in Hashimoto's disease--the most common organ-specific autoimmune disease. Epitope mapping studies have shown that the autoimmune response to TPO is directed mainly at two surface regions on the molecule: immunodominant regions A and B (IDR-A, and IDR-B). TPO(More)
The propeptide of human thyroid peroxidase is not required for its cellular, enzymatic or immunological activity Thyroid Peroxidase (TPO), a dimeric, membrane-bound glycoprotein found in the thyroid follicular lumen, catalyses the biosynthesis of thyroxine, and is also a major autoanti-gen in autoimmune thyroid disease (AITD). TPO molecules undergo(More)
SUMMARY The cloning and expression of TPO as a recombinant protein has allowed progress on the characterisation of the autoantigenic epitopes recognised by autoantibodieJ. fhe main immunogenic region of the molecule recognised by autoaniibodies has been localized to the carboxyl terminal. Multiple sequence alignment and secondary structure prediction(More)
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