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NKG2D is an activating receptor expressed on all human NK cells and a subset of T cells. In cytolytic conjugates between NK cells and target cells expressing its ligand MHC class I chain-related gene A, NKG2D accumulates at the immunological synapse with GM1-rich microdomains. Furthermore, NKG2D is specifically recruited to detergent-resistant membrane fractions upon ligation. However, in the presence of a strong inhibitory stimulus, NKG2D-mediated cytotoxicity can be intercepted, and recruitment of NKG2D to the immunological synapse and detergent-resistant membrane fractions is blocked. Also, downstream phosphorylation of Vav-1 triggered by NKG2D ligation is circumvented by coengaging inhibitory receptors. Thus, we propose that one way in which inhibitory signaling can control NKG2D-mediated activation is by blocking its recruitment to GM1-rich membrane domains. The accumulation of activating NK cell receptors in GM1-rich microdomains may provide the necessary platform from which stimulatory signals can proceed.

Original publication

DOI

10.4049/jimmunol.178.9.5606

Type

Journal article

Journal

Journal of immunology (Baltimore, Md. : 1950)

Publication Date

05/2007

Volume

178

Pages

5606 - 5611

Addresses

Institute for Immunology, University Heidelberg, Im Neuenheimer Feld 305, Heidelberg, Germany.

Keywords

Killer Cells, Natural, Cells, Cultured, Membrane Microdomains, Humans, Actins, G(M1) Ganglioside, Receptors, Immunologic, Lymphocyte Activation, Phosphorylation, Proto-Oncogene Proteins c-vav, Receptors, KIR2DL1, Receptors, Natural Killer Cell, NK Cell Lectin-Like Receptor Subfamily K