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

الملخص EN

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.