Cis association of Ly49A with MHC class I restricts natural killer cell inhibition

Marie Agnès Doucey; Léonardo Scarpellino; Jacques Zimmer; Philippe Guillaume; Immanuel F. Luescher; Claude Bron; Werner Held

doi:10.1038/ni1043

Cis association of Ly49A with MHC class I restricts natural killer cell inhibition

Marie Agnès Doucey, Léonardo Scarpellino, Jacques Zimmer, Philippe Guillaume, Immanuel F. Luescher, Claude Bron, Werner Held^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Research › peer-review

161 Citations (Scopus)

Abstract

Natural killer (NK) cell function is negatively regulated by inhibitory receptors interacting with major histocompatibility complex class I molecules expressed on target cells. Here we show that the inhibitory Ly49A NK cell receptor not only binds to its H-2D^d ligand expressed on potential target cells (in trans) but also is constitutively associated with H-2D^d in cis (on the same cell). Cis association and trans interaction occur through the same binding site. Consequently, cis association restricts the number of Ly49A receptors available for binding of H-2D^d on target cells and reduces NK cell inhibition through Ly49A. By lowering the threshold at which NK cell activation exceeds NK cell inhibition, cis interaction allows optimal discrimination of normal and abnormal host cells.

Original language	English
Pages (from-to)	328-336
Number of pages	9
Journal	Nature Immunology
Volume	5
Issue number	3
DOIs	https://doi.org/10.1038/ni1043
Publication status	Published - Mar 2004
Externally published	Yes

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title = "Cis association of Ly49A with MHC class I restricts natural killer cell inhibition",

abstract = "Natural killer (NK) cell function is negatively regulated by inhibitory receptors interacting with major histocompatibility complex class I molecules expressed on target cells. Here we show that the inhibitory Ly49A NK cell receptor not only binds to its H-2Dd ligand expressed on potential target cells (in trans) but also is constitutively associated with H-2Dd in cis (on the same cell). Cis association and trans interaction occur through the same binding site. Consequently, cis association restricts the number of Ly49A receptors available for binding of H-2Dd on target cells and reduces NK cell inhibition through Ly49A. By lowering the threshold at which NK cell activation exceeds NK cell inhibition, cis interaction allows optimal discrimination of normal and abnormal host cells.",

author = "Doucey, {Marie Agn{\`e}s} and L{\'e}onardo Scarpellino and Jacques Zimmer and Philippe Guillaume and Luescher, {Immanuel F.} and Claude Bron and Werner Held",

note = "Funding Information: We thank Fr{\'e}d{\'e}ric Levy, Ed Palmer, Olivier Michielin, J{\'e}r{\^o}me Coudert and Jean-Charles Cerottini for discussions. Supported in part by the Swiss National Science Foundation (W.H. and C.B.), the Swiss Cancer League (W.H.) and the Giorgi-Cavalieri-Foundation (C.B.).",

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AU - Doucey, Marie Agnès

AU - Scarpellino, Léonardo

AU - Zimmer, Jacques

AU - Guillaume, Philippe

AU - Luescher, Immanuel F.

AU - Bron, Claude

AU - Held, Werner

N1 - Funding Information: We thank Frédéric Levy, Ed Palmer, Olivier Michielin, Jérôme Coudert and Jean-Charles Cerottini for discussions. Supported in part by the Swiss National Science Foundation (W.H. and C.B.), the Swiss Cancer League (W.H.) and the Giorgi-Cavalieri-Foundation (C.B.).

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N2 - Natural killer (NK) cell function is negatively regulated by inhibitory receptors interacting with major histocompatibility complex class I molecules expressed on target cells. Here we show that the inhibitory Ly49A NK cell receptor not only binds to its H-2Dd ligand expressed on potential target cells (in trans) but also is constitutively associated with H-2Dd in cis (on the same cell). Cis association and trans interaction occur through the same binding site. Consequently, cis association restricts the number of Ly49A receptors available for binding of H-2Dd on target cells and reduces NK cell inhibition through Ly49A. By lowering the threshold at which NK cell activation exceeds NK cell inhibition, cis interaction allows optimal discrimination of normal and abnormal host cells.

AB - Natural killer (NK) cell function is negatively regulated by inhibitory receptors interacting with major histocompatibility complex class I molecules expressed on target cells. Here we show that the inhibitory Ly49A NK cell receptor not only binds to its H-2Dd ligand expressed on potential target cells (in trans) but also is constitutively associated with H-2Dd in cis (on the same cell). Cis association and trans interaction occur through the same binding site. Consequently, cis association restricts the number of Ly49A receptors available for binding of H-2Dd on target cells and reduces NK cell inhibition through Ly49A. By lowering the threshold at which NK cell activation exceeds NK cell inhibition, cis interaction allows optimal discrimination of normal and abnormal host cells.

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Cis association of Ly49A with MHC class I restricts natural killer cell inhibition

Abstract

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