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

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

Simo Xia, Yijie Tao, Likun Cui, Yizhi Yu, Sheng Xu

J Immunol Res. 2019 Sep 9;2019:5370706.

PMID: 31583257

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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