Presentation description

Molecular mimicry is a proposed mechanism by which an infectious agent may trigger an autoimmune response. This occurs when foreign peptides exhibit sequence or structural similarity to self-antigens, leading to cross-reactive immune activation. Identifying potential molecular mimics is critical to understanding the exacerbation of autoimmune disorders, including type 1 diabetes mellitus (T1DM). Human herpesvirus 6B (HHV-6B), a ubiquitous virus implicated in several autoimmune conditions, has been epidemiologically linked to increased T1DM risk, especially following early-life infection. However, the association between HHV-6B and TIDM remains unclear in existing literature, as HHV-6B epitopes listed in the Immune Epitope Database (IEDB) show limited sequence homology with known T1DM autoantigens. Following primary infection, HHV-6B establishes lifelong latency, and may reactivate and cause further complications to a wide range of cell types.

This study investigates the potential for HHV-6B epitopes to act as molecular mimics of T1DM-associated antigens, exploring a possible link between HHV-6B infection with T1DM onset. Three-dimensional structures of HHV-6B and T1DM epitopes were compared using Boltz-1, an open-source protein structure modeling tool. Structural similarity was assessed using root mean square deviation (RMSD) and electrostatic potential calculations in USCF ChimeraX. A previously studied HHV-6B epitope demonstrated strong structural alignment with T1D epitopes (RMSD < 1.0 Å) and exhibited comparable electrostatic surface potentials. When modeled in complex with a key Human Leukocyte Antigen (HLA) molecule, the HHV-6B and T1D epitopes adopted overlapping conformations, supporting the potential for T cell cross-reactivity. These findings demonstrate through structural modeling that HHV-6B may act as a molecular mimic contributing to autoimmune disease in genetically susceptible individuals. Future work involving molecular docking to investigate other HHV-6B epitopes will aid in early detection and preventative strategies for autoimmune conditions.