Influenza virus infection augments NK cell inhibition through reorganization of major histocompatibility complex class I proteins.
The killing by natural killer (NK) cells is regulated by inhibitory, costimulatory, and activating receptors. The inhibitory receptors recognize mainly major histocompatibility complex (MHC) class I molecules, while the activating NK receptors recognize stress-induced ligands and viral products. Thus, changes in the expression of the various inhibitory and activating ligands will determine whether target cells will be killed or protected. Here, we demonstrate that after influenza virus infection the binding of the two NK inhibitory receptors, KIR2DL1 and the LIR1, to the infected cells is specifically increased. The increased binding occurs shortly after the influenza virus infection, prior to the increased recognition of the infected cells by the NK activating receptor, NKp46. We also elucidate the mechanism responsible for this effect and demonstrate that, after influenza virus infection, MHC class I proteins redistribute on the cell surface and accumulate in the lipid raft microdomains. Such redistribution allows better recognition by the NK inhibitory receptors and consequently increases resistance to NK cell attack. In contrast, T-cell activity was not influenced by the redistribution of MHC class I proteins. Thus, we present here a novel mechanism, developed by the influenza virus, of inhibition of NK cell cytotoxicity, through the reorganization of MHC class I proteins on the cell surface.
The Lautenberg Center for General and Tumor Immunology, The Hebrew University Hadassah Medical School, Jerusalem 91120, Israel.
Hagit
H
Achdout
Irit
I
Manaster
Ofer
O
Mandelboim
D000911:Antibodies, Monoclonal / Q000737:chemistry; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000821:virology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007252:Influenza Vaccines / Q000737:chemistry*; D007251:Influenza, Human / Q000097:blood*; D007694:Killer Cells, Natural / Q000378:metabolism*; D008024:Ligands; D021962:Membrane Microdomains / Q000378:metabolism / Q000821:virology; D055627:Natural Cytotoxicity Triggering Receptor 1; D009975:Orthomyxoviridae / Q000378:metabolism*; D011485:Protein Binding; D011971:Receptors, Immunologic / Q000737:chemistry; D013601:T-Lymphocytes / Q000821:virology; D014764:Viral Proteins / Q000737:chemistry
D000911:Antibodies, Monoclonal; D015395:Histocompatibility Antigens Class I; D007252:Influenza Vaccines; D008024:Ligands; C112260:NCR1 protein, human; D055627:Natural Cytotoxicity Triggering Receptor 1; D011971:Receptors, Immunologic; D014764:Viral Proteins