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Yotam Bar On - Uncovering the role of immune checkpoints in viral infection: Influenza hemagglutinin a novel ligand for the inhibitory immune receptor LAG-3

Immune checkpoints play a pivotal role in regulating the immune system activity. These checkpoints encompass molecules and pathways that act as inhibitory regulators on the immune system. The seminal findings  that tumor cells can exploit immune checkpoints to impede anti-tumor immunity has transformed cancer immunotherapy and immune checkpoint blockade has emerged as a highly successful approach in restoring anti-tumor immune functions and treating cancer patients. However, our understanding of the involvement of immune checkpoints in viral infections is comparatively limited. In our quest to dissect the role of immune checkpoint receptor during acute viral infection we demonstrated the inhibitory receptor LAG-3 can recognize influenza virus-infected epithelial cells. We further show that this recognition is mediated by the direct binding of LAG-3 to influenza virus hemagglutinin. Moreover, we uncovered the mechanism of LAG-3-hemagglutinin interaction and the possible effect of LAG-3-hemagglutinin interaction on the antiviral immune response. The long-term goal of this proposed study in to provide a thorough evaluation of the role played by LAG-3 in the context of acute viral infections and immunization processes. We will examining how the immune checkpoint receptor LAG-3 influence the intricate dynamics between cytotoxic T cells and influenza virus-infected cells. Additionally,we aim to assess the involvement of these inhibitory pathways in vaccination against influenza viruses. Altogether, this proposed study will facilitate a thorough understanding of the role of LAG-3 in the modulating the antiviral immune response.

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