COMPARATIVE MAPPING OF CLONED HUMAN AND MURINE ANTITHYROGLOBULIN ANTIBODIES - RECOGNITION BY HUMAN-ANTIBODIES OF AN IMMUNODOMINANT REGION

Antibodies (Ab) to thyroglobulin (Tg) are common in patients with auto immune thyroid diseases, but it is currently unclear how Tg Ab are inv olved in the pathology of autoimmune thyroid disease. We have previous ly reported the isolation of immunoglobulin G (IgG)kappa and IgG lambd a Fab from phage display combinatorial libraries from the cervical lym ph node of a single Hashimoto's thyroiditis patient with a high anti-T g titer. Sequence analysis of these Fab indicated a restricted heavy c hain usage with a nonrestricted light chain usage, with Fab inhibiting the binding of patient Tg Ab by between 39% and 79%. Comparative mapp ing of nine each of these IgG kappa and IgG lambda Fab, and the patien t serum from whom the Fab were derived, is described here, using a pan el of 10 murine monoclonal antibodies (Mab) to human thyroglobulin (hT g). The Fab interacted principally with mAb defining the overlapping a ntigenic domains I and IV, previously characterized as the region reco gnized by the majority of patient serum Tg Ab. Tg Ab from serum of the patient from whom the Fab were derived were also directed at this reg ion, suggesting that the Fab are representative of the Tg Ab present i n this patient.