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Nat Immunol. 2002 Dec;3(12):1142-9. Epub 2002 Nov 11.

Selective associations with signaling proteins determine stimulatory versus costimulatory activity of NKG2D.

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1
Department of Molecular and Cell Biology and Cancer Research Laboratory, University of California, Berkeley, CA 94720-3200, USA.

Erratum in

  • Nat Immunol. 2004 Jun;5(6):658.

Abstract

Optimal lymphocyte activation requires the simultaneous engagement of stimulatory and costimulatory receptors. Stimulatory immunoreceptors are usually composed of a ligand-binding transmembrane protein and noncovalently associated signal-transducing subunits. Here, we report that alternative splicing leads to two distinct NKG2D polypeptides that associate differentially with the DAP10 and KARAP (also known as DAP12) signaling subunits. We found that differential expression of these isoforms and of signaling proteins determined whether NKG2D functioned as a costimulatory receptor in the adaptive immune system (CD8+ T cells) or as both a primary recognition structure and a costimulatory receptor in the innate immune system (natural killer cells and macrophages). This strategy suggests a rationale for the multisubunit structure of stimulatory immunoreceptors.

Comment in

PMID:
12426565
DOI:
10.1038/ni858
[Indexed for MEDLINE]

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