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 journalArticleResearchpeer-review

159 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)328-336
Number of pages9
JournalNature Immunology
Issue number3
Publication statusPublished - Mar 2004
Externally publishedYes


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