Immunosynapse formation coincides with rapid activation of NK cells by syngeneic T cells and correlates with clustering of MHC class I.
T cells cultured for 3 h with antigen-presenting cells (APCs) stimulated syngeneic IL-2-activated NK cells as measured via a standard chromium-release assay. Discrete caps containing both TCR and MHC-I had formed on the surface of these activated T cells. When conjugates were formed between NK cells and these activated T cells, >80% of the contact sites were in the MHC-I(dim) region outside the TCR-MHC-I cap. Stimulation with phorbol myristate acetate plus Ionomycin, which bypasses the need for cell surface events during activation, did not induce either cap formation or NK cell activation. Further, the addition of the protein transport inhibitor Brefeldin A did not block activation of NK cells. MHC-I is the major inhibitory ligand recognized by NK cells. One possible mechanism for the activation of NK cells by TCR-MHC-I-capped T cells is that aggregation of MHC-I into one region leaves the remaining T cell surface denuded of ligands for NK-inhibitory receptors. As a test of this hypothesis, we aggregated MHC-I on T cells with plate-bound anti-MHC-I mAb. This treatment conferred upon the T cells the capacity to activate NK cells, suggesting that MHC-I clustering could contribute to the observed phenomenon.
Rabinovich
Brian A
BA
Amgen Washington, 1201 Amgen Court West, Seattle, WA 98119, USA.
Li
Jennifer
J
Hurren
Rose
R
Miller
Richard G
RG
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D020126:Brefeldin A / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism*; D007376:Interleukin-2; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; D007476:Ionophores; D011500:Protein Synthesis Inhibitors; D011948:Receptors, Antigen, T-Cell; D020126:Brefeldin A; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate