H-2D ligand expression by Ly49A+ natural killer (NK) cells precludes ligand uptake from environmental cells: implications for NK cell function.


Autoria(s): Zimmer J.; Ioannidis V.; Held W.
Data(s)

2001

Resumo

To study the adaptation of natural killer (NK) cells to their major histocompatibility complex (MHC) class I environment we have established a novel mouse model with mosaic expression of H-2D(d) using a Cre/loxP system. In these mice, we noticed that NK cells expressing the inhibitory receptor for D(d), Ly49A, were specifically underrepresented among cells with low D(d) levels. That was due to the acquisition of D(d) molecules by the Ly49A+ NK cells that have lost their D(d) transgene. The uptake of H-2D molecules via the Ly49A receptor was restricted to strong ligands of Ly49A. Surprisingly, when Ly49A+ NK cells were D(d+), uptake of the alternative ligand D(k) was not detectable. Similarly, one anti-Ly49A mAb (A1) bound inefficiently when Ly49A was expressed on D(d+) NK cells. Concomitantly, functional assays demonstrated a reduced capacity of Ly49A to inhibit H-2(b)D(d) as compared with H-2(b) NK cells, rendering Ly49A+ NK cells in D(d+) mice particularly reactive. Minor reductions of D(d) levels and/or increases of activating ligands on environmental cells may thus suffice to abrogate Ly49A-mediated NK cell inhibition. The mechanistic explanation for all these phenomena is likely the partial masking of Ly49A by D(d) on the same cell via a lateral binding site in the H-2D(d) molecule.

Identificador

https://serval.unil.ch/?id=serval:BIB_18299

isbn:0022-1007

pmid:11714759

doi:10.1084/jem.194.10.1531

isiid:000172351700014

http://my.unil.ch/serval/document/BIB_18299.pdf

http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_182993

Idioma(s)

en

Direitos

info:eu-repo/semantics/openAccess

Fonte

The Journal of Experimental Medicine, vol. 194, no. 10, pp. 1531-1539

Palavras-Chave #Animals; Antigens, Ly; Carrier Proteins/physiology; H-2 Antigens/metabolism; Killer Cells, Natural/physiology; Lectins, C-Type; Ligands; Membrane Proteins/physiology; Mice; Mice, Inbred C57BL; Mice, Transgenic; NK Cell Lectin-Like Receptor Subfamily A; Receptors, NK Cell Lectin-Like
Tipo

info:eu-repo/semantics/article

article