Dataset Information

Minimal requirement for induction of natural cytotoxicity and intersection of activation signals by inhibitory receptors.

ABSTRACT: Natural killer (NK) cells provide innate control of infected and neoplastic cells. Multiple receptors have been implicated in natural cytotoxicity, but their individual contribution remains unclear. Here, we studied the activation of primary, resting human NK cells by Drosophila cells expressing ligands for receptors NKG2D, DNAM-1, 2B4, CD2, and LFA-1. Each receptor was capable of inducing inside-out signals for LFA-1, promoting adhesion, but none induced degranulation. Rather, release of cytolytic granules required synergistic activation through coengagement of receptors, shown here for NKG2D and 2B4. Although engagement of NKG2D and 2B4 was not sufficient for strong target cell lysis, collective engagement of LFA-1, NKG2D, and 2B4 defined a minimal requirement for natural cytotoxicity. Remarkably, inside-out signaling induced by each one of these receptors, including LFA-1, was inhibited by receptor CD94/NKG2A binding to HLA-E. Strong inside-out signals induced by the combination of NKG2D and 2B4 or by CD16 could overcome CD94/NKG2A inhibition. In contrast, degranulation induced by these receptors was still subject to inhibition by CD94/NKG2A. These results reveal multiple layers in the activation pathway for natural cytotoxicity and that steps as distinct as inside-out signaling to LFA-1 and signals for granule release are sensitive to inhibition by CD94/NKG2A.

SUBMITTER: Bryceson YT

PROVIDER: S-EPMC2756125 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Minimal requirement for induction of natural cytotoxicity and intersection of activation signals by inhibitory receptors.

Bryceson Yenan T YT Ljunggren Hans-Gustaf HG Long Eric O EO

Blood 20090723 13

Natural killer (NK) cells provide innate control of infected and neoplastic cells. Multiple receptors have been implicated in natural cytotoxicity, but their individual contribution remains unclear. Here, we studied the activation of primary, resting human NK cells by Drosophila cells expressing ligands for receptors NKG2D, DNAM-1, 2B4, CD2, and LFA-1. Each receptor was capable of inducing inside-out signals for LFA-1, promoting adhesion, but none induced degranulation. Rather, release of cytoly ...[more]

PMID: 19628705

Similar Datasets

Project description:The origin of the signals that induce the differentiation of the central nervous system (CNS) is a long-standing question in vertebrate embryology. Here we show that Xenopus neural induction starts earlier than previously thought, at the blastula stage, and requires the combined activity of two distinct signaling centers. One is the well-known Nieuwkoop center, located in dorsal-vegetal cells, which expresses Nodal-related endomesodermal inducers. The other is a blastula Chordin- and Noggin-expressing (BCNE) center located in dorsal animal cells that contains both prospective neuroectoderm and Spemann organizer precursor cells. Both centers are downstream of the early beta-Catenin signal. Molecular analyses demonstrated that the BCNE center was distinct from the Nieuwkoop center, and that the Nieuwkoop center expressed the secreted protein Cerberus (Cer). We found that explanted blastula dorsal animal cap cells that have not yet contacted a mesodermal substratum can, when cultured in saline solution, express definitive neural markers and differentiate histologically into CNS tissue. Transplantation experiments showed that the BCNE region was required for brain formation, even though it lacked CNS-inducing activity when transplanted ventrally. Cell-lineage studies demonstrated that BCNE cells give rise to a large part of the brain and retina and, in more posterior regions of the embryo, to floor plate and notochord. Loss-of-function experiments with antisense morpholino oligos (MO) showed that the CNS that forms in mesoderm-less Xenopus embryos (generated by injection with Cerberus-Short [CerS] mRNA) required Chordin (Chd), Noggin (Nog), and their upstream regulator beta-Catenin. When mesoderm involution was prevented in dorsal marginal-zone explants, the anterior neural tissue formed in ectoderm was derived from BCNE cells and had a complete requirement for Chd. By injecting Chd morpholino oligos (Chd-MO) into prospective neuroectoderm and Cerberus morpholino oligos (Cer-MO) into prospective endomesoderm at the 8-cell stage, we showed that both layers cooperate in CNS formation. The results suggest a model for neural induction in Xenopus in which an early blastula beta-Catenin signal predisposes the prospective neuroectoderm to neural induction by endomesodermal signals emanating from Spemann's organizer.

Dataset Information

Minimal requirement for induction of natural cytotoxicity and intersection of activation signals by inhibitory receptors.

Publications

Minimal requirement for induction of natural cytotoxicity and intersection of activation signals by inhibitory receptors.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets