MHC Class i Molecules Exacerbate Viral Infection by Disrupting Type i Interferon Signaling

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Abstract

MHC class I molecules are key in the presentation of antigen and initiation of adaptive CD8+ T cell responses. In addition to its classical activity, MHC I may possess nonclassical functions. We have previously identified a regulatory role of MHC I in TLR signaling and antibacterial immunity. However, its role in innate antiviral immunity remains unknown. In this study, we found a reduced viral load in MHC I-deficient macrophages that was independent of type I IFN production. Mechanically, MHC I mediated viral suppression by inhibiting the type I IFN signaling pathway, which depends on SHP2. Cross-linking MHC I at the membrane increased SHP2 activation and further suppressed STAT1 phosphorylation. Therefore, our data revealed an inhibitory role of MHC I in type I IFN response to viral infection and expanded our understanding of MHC I and antigen presentation.

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Xia, S., Tao, Y., Cui, L., Yu, Y., & Xu, S. (2019). MHC Class i Molecules Exacerbate Viral Infection by Disrupting Type i Interferon Signaling. Journal of Immunology Research, 2019. https://doi.org/10.1155/2019/5370706

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