Evaluating CTLA-4 Antibody–Antigen Binding as a Model for Targeted Immunosuppressant Delivery in Hashimoto’s Thyroiditis

Autoimmune disorders such as Hashimoto's thyroiditis lack curative treatments, only therapeutic agents that treat symptoms very broadly and dampen the entire immune system, including healthy cells. Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4) is an immune checkpoint receptor expressed on T cells, and in Hashimoto's thyroiditis the overexpression of CTLA-4 on dysfunctional immune cells is a key factor in disease progression. Here, we evaluated CTLA-4 antibody-antigen binding to specifically treat dysfunctional cells. Protein-protein docking identified Cluster 0 as the most stable pose (energy score -334), ChimeraX showed a buried surface area of 2,136 Ų and 1,023 hydrogen bonds, and in vitro assays confirmed binding.