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Papers by Allison Knight
Springer Seminars in Immunopathology, 1982
Two decades of investigation of the TSH receptor as an autoantigen have led not only to elucidati... more Two decades of investigation of the TSH receptor as an autoantigen have led not only to elucidation of the pathogenesis of Graves' disease but also to a general theory of autoimmunity. The H-gene theory [10] indicates a strategy for the treatment of autoimmune disease by intervention in the network of paratope-idiotope interactions controlling clonal deletions [54]. In the past 10 years, investigation of the hormone-binding function of the receptor has demonstrated the mechanism of action of the thyroid-stimulating autoantibodies, and provided the basis for the convenient radioreceptor assay of TSaab. This technique has yet to achieve its apparent potential, but the widely-used methodology has been essentially unchanged since 1973 [80]. Recent work has shown improvements in receptor abundance, affinity, and specificity are achievable by manipulation of ionic strength [100], observations which may provide the key to eliminating the major failings of the radioreceptor assay, namely sensitivity and the nonspecific effect of normal control globulins. Since the amounts of TSH receptor in thyroid tissue are minute, it is unlikely that purification to homogeneity will be achieved in the near future. Nevertheless, the recent demonstrations of receptor heterogeneity [37, 79] and the possible role of gangliosides of known simple structure in receptor function suggest that new and important insights into hormone-receptor interaction may still be forthcoming from the study of TSH receptors.
Springer Seminars in Immunopathology, 1982
Two decades of investigation of the TSH receptor as an autoantigen have led not only to elucidati... more Two decades of investigation of the TSH receptor as an autoantigen have led not only to elucidation of the pathogenesis of Graves' disease but also to a general theory of autoimmunity. The H-gene theory [10] indicates a strategy for the treatment of autoimmune disease by intervention in the network of paratope-idiotope interactions controlling clonal deletions [54]. In the past 10 years, investigation of the hormone-binding function of the receptor has demonstrated the mechanism of action of the thyroid-stimulating autoantibodies, and provided the basis for the convenient radioreceptor assay of TSaab. This technique has yet to achieve its apparent potential, but the widely-used methodology has been essentially unchanged since 1973 [80]. Recent work has shown improvements in receptor abundance, affinity, and specificity are achievable by manipulation of ionic strength [100], observations which may provide the key to eliminating the major failings of the radioreceptor assay, namely sensitivity and the nonspecific effect of normal control globulins. Since the amounts of TSH receptor in thyroid tissue are minute, it is unlikely that purification to homogeneity will be achieved in the near future. Nevertheless, the recent demonstrations of receptor heterogeneity [37, 79] and the possible role of gangliosides of known simple structure in receptor function suggest that new and important insights into hormone-receptor interaction may still be forthcoming from the study of TSH receptors.