The interaction with H-2D(d) in cis is associated with a conformational change in the Ly49A NK cell receptor.

Frontiers in Immunology
Jonathan BackWerner Held

Abstract

Mouse natural killer (NK) cells express Ly49 family receptors that recognize major histocompatibility complex class I (MHC-I) molecules. By interacting with MHC-I molecules expressed on other cells (in trans), inhibitory Ly49 receptors prevent the NK cell-mediated killing of normal cells. In addition, some Ly49 receptors have the unusual property to also interact with MHC-I molecules expressed by the NK cell itself (in cis). cis Binding sequesters a significant fraction of the NK cells' Ly49 receptors, reducing the number of receptors available for trans binding. This lowers the threshold at which NK cell activation exceeds inhibition rendering NK cells more sensitive. It is unclear how Ly49 receptors can bind MHC-I in trans and in cis using the same binding site. We have proposed that this is mediated by two distinct conformations of Ly49 receptors. Here we have tested this model by inferring the distance between the ligand-binding domain of Ly49A and the cell membrane using fluorescence resonance energy transfer (FRET). Consistent with the concept, reducing the distance between the ligand-binding domain of Ly49A and the cell membrane, by shortening the Ly49A stalk, resulted in a substantially increased FRET. The co-expression...Continue Reading

Citations

Aug 8, 2014·Frontiers in Immunology·Stéphanie BessolesWerner Held
May 2, 2015·European Journal of Immunology·Kristin LampeKasper Hoebe
Jan 2, 2021·Frontiers in Immunology·Elke M MuntjewerffNatalia H Revelo
Nov 11, 2019·Journal of Molecular Biology·Yang LiuImmanuel F Luescher

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Methods Mentioned

BETA
fluorescence resonance
FRET
FCS
flow cytometry
FACS

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