title: FasL and the NKG2D receptor are required for the secretion of the Tag7/PGRP-S-Hsp70 complex by the cytotoxic CD8+lymphocytes.
abstract: Tag7 (PGRP-S or PGLYRP1), while possessing an antimicrobial activity, also exhibits an antitumor effect when in complex with the major heat shock protein Hsp70. The cytotoxic Tag7-Hsp70 complex is secreted by lymphocytes after interaction with the HLA-negative tumors. Previously, we have shown that IL-2 induces formation of the CD4+and CD8+cytotoxic subpopulations of human lymphocytes, which kill tumor cells through the FasL-Fas interaction. Here, we show that only the CD8+T cells are able to secrete the Tag7-Hsp70 complex. For its secretion the same proteins on the surface of the lymphocytes and target cells, which are involved in the contact lysis, are necessary as well. The interaction of Fas receptor with FasL leads to an activation of the Tag7-Hsp70 complex in the lymphocyte membrane fraction, and here FasL acts as a receptor that induces intracellular signaling in lymphocytes. An interaction of the MicA stress ligand with the NKG2D receptor is necessary for the release of this cytotoxic complex. It is possible, that CD8+T lymphocytes interacting with a target cell can both carry out the contact killing of these cells and to secrete the cytotoxic factor. © 2016 IUBMB Life, 69(1):30-36, 2017.
authors.affiliation: Institute of Gene Biology RAS, Vavilova 34/5, Moscow, 119334, Russia.
authors.forename: Lidia P
authors.initials: LP
authors.lastname: Sashchenko
authors.affiliation: Institute of Gene Biology RAS, Vavilova 34/5, Moscow, 119334, Russia.
authors.forename: Elena A
authors.initials: EA
authors.lastname: Romanova
authors.affiliation: Institute of Gene Biology RAS, Vavilova 34/5, Moscow, 119334, Russia.
authors.forename: Olga K
authors.initials: OK
authors.lastname: Ivanova
authors.affiliation: Institute of Gene Biology RAS, Vavilova 34/5, Moscow, 119334, Russia.
authors.forename: Tatiana N
authors.initials: TN
authors.lastname: Sharapova
authors.affiliation: Institute of Gene Biology RAS, Vavilova 34/5, Moscow, 119334, Russia.
authors.forename: Denis V
authors.initials: DV
authors.lastname: Yashin
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000235:genetics*; D003602:Cytotoxicity, Immunologic; D053222:Fas Ligand Protein / Q000235:genetics* / Q000276:immunology; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D020014:K562 Cells; D051379:Mice; D046912:Multiprotein Complexes / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000235:genetics* / Q000276:immunology
chemical_list: D016207:Cytokines; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; C099187:MHC class I-related chain A; D046912:Multiprotein Complexes; D055655:NK Cell Lectin-Like Receptor Subfamily K; C491878:PGLYRP1 protein, human
keywords: Fas; FasL; HLA-negative tumor cells; MicA; NKG2D; Tag7-Hsp70 cytotoxic complex; cytotoxic CD8+ T lymphocytes