Thyroid iodide transporter: local sequence homologies with thyroid autoantigens

Here we show the existence of local amino acid (aa) sequence homologies between rat thyroid iodide transporter (Na+/I- symporter or NIS), whose gene was recently cloned, and known human thyroid autoantigens [thyroglobulin (Tg), thyroid peroxidase (TPO) and thyrotropin receptor (TSHR)] NIS sequences corresponding to the fourth (aa 264-282) and fifth extracellular loop (aa 386-414) are 15 to 40% identical and 30 to 60% similar to sequences corresponding to known or putative epitopes of Tg, TPO and TSHR. The sixth extracellular loop (aa 465-485) beared homology (44%, identity, 52% similarity) only to a region of Tg which flanks one of its immunodominant domains. Sequences of thyroid autoantigens other than NIS shared homology, especially Tg and TPO. We conclude that in all likelihood NIS is an additional thyroid antigen, which shares common epitopes with the other thyroid autoantigens. Addendum: A study in abstract form appeared after submission of our paper finds experimental evidence for the antigenicity of two extracellular segments (aa 262-280 and 468-487) and of a portion of the intracellular C-terminus (aa 560-579).