Evidence for a Potential Common T-Cell Epitope Between Human Thyroid Peroxidase and Human Thyroglobulin with Implications for the Pathogenesis of Autoimmune Thyroid Disease

Abstract

In order to explore the possibility that, in autoimmune thyroid disease, anti-thyroglobulin (Tg) and anti-thyroid peroxidase (TPO) antibodies arise concurrently because they share a common T-cell epitope, we performed a detailed comparative analysis of the cDNA nucleotide sequences corresponding to these two genes. We discovered an 8 amino acid region (Leu-Ser-Glu-Asp-Leu-Leu-Ser- Ile in human TPO) in which there were 6 identical and 2 conserved amino acid residues when compared with human Tg. This remarkably similar region is near the amino-terminus of human TPO (residues 119–126) and the carboxyl-terminus of human Tg (residues 2763–2770). A second feature of interest was that this region of homology conforms to the Rothbard algorithm for a T-cell epitope. Third, probing of the Swiss-protein data bank (10,008 proteins containing 2,952,765 amino acids) with the human TPO region revealed greater homology for human Tg than for any other eukaryotic protein. Two bacterial proteins (E. coli aminopeptidase N and stringent starvation protein) had higher homology scores from human TPO than did human Tg. Our findings provide circumstantial evidence that human TPO and human Tg, and possibly certain bacterial proteins, do indeed share common T-cell epitopes that may play a role in the pathogenesis of autoimmune thyroid disease.