Soluble Antigen Arrays Alter the Response of Epitope-Specific Diabetogenic T Cells

Type 1 diabetes (T1D) is driven by autoreactive T cells, which destroy insulin-producing β cells. Antigen-specific immunotherapies (ASITs) aim to restore immune tolerance while avoiding the broad immunosuppression of current therapies. Soluble antigen arrays (SAgAs) are multivalent antigen constructs built on a low-molecular-weight hyaluronic acid (HA) backbone, previously validated in preclinical models. Here, we generated SAgAs displaying human T1D autoantigen epitopes, including Insulin B:9-23 (InsB:9-23) and a hybrid insulin peptide (HIP), alongside a hemagglutinin (HAg):306-318 control. We confirmed their structure, valency, and ability to engage human epitope-specific T cell clones. Both InsB:9-23-SAgA and HIP-SAgA demonstrated strong specificity, supporting their utility as T cell probes and potential candidates for ASIT in T1D.