Enhanced recognition of human NK receptors after influenza virus infection.
The NK cell cytotoxic activity is regulated by both inhibitory and activating NK receptors. Thus, changes in the expression levels and in the affinity or avidity of those receptors will have a major effect on the killing of target cells. In this study, we demonstrate that the binding of NK-inhibitory receptors is enhanced after influenza virus infection. Surprisingly, however, no change in the level of class I MHC protein expression was observed on the surface of the infected cells. The increased binding was general, because it was observed in both the killer cell Ig-like receptor 2 domain long tail 1 and leukocyte Ig-like receptor-1. The increased binding was functional, was not dependent on the interaction with viral hemagglutinin-neuraminidase, was not dependent on the glycosylation site, and was not abolished after mutating the transmembrane or cytosolic portions of the class I MHC proteins. Confocal microscopy experiments showed increased binding of NK receptor-coated beads to infected cells expressing the appropriate class I MHC proteins. In addition, specific cell-free bead aggregates covered with class I MHC proteins were observed only in infected cells. We therefore suggest that the influenza virus use a novel mechanism for the inhibition of NK cell activity. This mechanism probably involves the generation of class I MHC complexes in infected cells that cause increased recognition of NK receptors.
Achdout
Hagit
H
The Lautenberg Center for General and Tumor Immunology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Arnon
Tal I
TI
Markel
Gal
G
Gonen-Gross
Tsufit
T
Katz
Gil
G
Lieberman
Niva
N
Gazit
Roi
R
Joseph
Aviva
A
Kedar
Eli
E
Mandelboim
Ofer
O
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D015236:HLA-C Antigens / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D006801:Humans; D009980:Influenza A virus / Q000276:immunology* / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008863:Microspheres; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D054342:Receptors, KIR2DL1; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000378:metabolism; D029082:Sendai virus / Q000276:immunology; D013045:Species Specificity; D014162:Transfection; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000276:immunology
D015703:Antigens, CD; D015236:HLA-C Antigens; C039966:HLA-C*04 antigen; D007376:Interleukin-2; C105299:LILRB1 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D010446:Peptide Fragments; D011971:Receptors, Immunologic; D054342:Receptors, KIR2DL1; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins