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

评估 CTLA-4 抗体-抗原结合作为桥本甲状腺炎靶向免疫抑制剂递送模型

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Abstract

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.

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