CLONING AND CHARACTERIZATION OF MURINE THYROGLOBULIN CDNA

Thyroglobulin is used to induce in mice experimental autoimmune thyroi ditis (EAT), a model for Hashimoto thyroiditis. Because murine thyrogl obulin is a more potent inducer of EAT than heterologous thyroglobulin s, it has been hypothesized that it contains unique pathogenic epitope s. The validation of this hypothesis has been hampered by the lack of the murine thyroglobulin sequence, To identify murine-specific areas i n thyroglobulin, we cloned, by reverse transcriptase PCR, and sequence d the complete murine thyroglobulin cDNA, This encodes a polypeptide o f 2748 amino acids that is 73.5 and 71.8% identical to bovine and huma n thyroglobulin, respectively. Six regions are unique to each species, We also analyzed through EpiMer the sequences able to bind to the I-E -k major histocompatibility allele and, therefore, function as T cell epitopes. EpiMer analysis showed seven murine-specific T cell epitopes in thyroglobulin, The availability of the complete murine thyroglobul in sequence should promote the understanding of the pathogenesis and i mmunoregulation of EAT. (C) 1997 Academic Press.