ILT2/HLA-G interaction impairs NK-cell functions through the inhibition of the late but not the early events of the NK-cell activating synapse.
Natural killer (NK) cells play a crucial role in the antitumoral responses through cytolytic function and cytokine production. Expression of HLA-G at the surface of tumoral cells confers a protection against NK-cell cytolysis through its interaction with the ILT2 inhibitory receptor. Even though the role of this interaction on the inhibition of NK-cell cytotoxicity is well established, its effect on the molecular events occurring at the NK/target-cell synapse is not well characterized. We found that the interaction of the inhibitory receptor ILT2 with HLA-G inhibited the polarization of NK-cell lytic granules and the microtubule organizing center (MTOC) as well as the accumulation of filamentous actin (F-actin) at the area of contact. However, it did not affect the recruitment of the activatory receptor CD2 at the NK/target-cell interface. Even though CD2 was accumulated to the NK-cell synapse, the interaction of ILT2 with HLA-G efficiently inhibited intracellular calcium mobilization and IFN-gamma polarized production of NK cells. These results indicate that while the ILT2/HLA-G interaction leads to the inhibition of NK-cell functions, it displays differential effects on cytoskeleton reorganization and CD2 localization at the NK-cell synapse.-Favier, B., LeMaoult, J., Lesport, E., Carosella, E. D. ILT2/HLA-G interaction impairs NK-cell functions through the inhibition of the late but not the early events of the NK-cell-activating synapse.
CEA, I2BM Service de Recherches en Hemato-Immunologie, Institut Universitaire d'Hematologie, Hopital Saint Louis, 1 Avenue Claude Vellefaux, 75010 Paris, France. benoit.favier@cea.fr
Benoit
B
Favier
Joel
J
Lemaoult
Emilie
E
Lesport
Edgardo D
ED
Carosella
D000199:Actins / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism*; D018801:CD2 Antigens / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D005434:Flow Cytometry; D006680:HLA Antigens / Q000378:metabolism*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D054992:Immunological Synapses / Q000378:metabolism / Q000502:physiology*; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000378:metabolism / Q000502:physiology*; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D018613:Microscopy, Confocal; D018715:Microscopy, Video; D022101:Microtubule-Organizing Center / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D011971:Receptors, Immunologic / Q000378:metabolism*
D000199:Actins; D015703:Antigens, CD; D018801:CD2 Antigens; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; C105299:LILRB1 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D011971:Receptors, Immunologic; D007371:Interferon-gamma; D002118:Calcium