Predicted T-Cell and B-Cell Epitopes of NIS: Where Do Sjögren’s Syndrome and Hashimoto’s Thyroiditis Converge?

The sodium iodide symporter (NIS) is a key protein in thyroid function responsible for
iodine uptake, and it may be involved in the pathogenesis of autoimmune thyroiditis.
However, it is also expressed in the salivary glands, the primary target of autoreactive
cells in Sjögren’s syndrome (SS). Given the common link between the two diseases, we
computationally investigated whether the epitopes of NIS can trigger an immune response
leading to SS in Hashimoto’s thyroiditis (HT) patients genetically predisposed to both
diseases. The TepiTool 2016, ABCpred 2006, and DiscoTope 2.0 servers were used to
predict T-cell and B-cell epitopes by inputting the FASTA sequences and 3D structures of
NIS, thyroid peroxidase (TPO) and Ro60 Y RNA-binding protein (Ro60), which served
as reference antigens for HT and SS, respectively. T-cell epitopes were selected based on
their binding to a panel of human leukocyte antigen (HLA) alleles associated with both
SS and HT.We identified a total of 376 linear T-cell epitopes, 64 linear B-cell epitopes and
68 conformational B-cell epitopes of NIS. Compared to TPO, NIS T-cell epitopes showed
significantly lower affinity for HLA alleles (p < 0.0001), while no significant difference was
found compared to Ro60. While linear B-cell epitopes of NIS, TPO, and Ro60 showed
similar binding affinity, conformational epitopes of NIS were predicted to have higher
immunogenicity than Ro60 (p = 0.04), while no significant difference was found compared
to TPO. These pivotal findings, discovered by the methods of computer modeling, suggest
that NIS can potentially activate T cells and B cells in patients with genetic predisposition
to SS and HT and need to be confirmed by further laboratory studies.