Altered Phenotype and Function of Natural Killer Cells Expressing the Major Histocompatibility Complex Receptor Ly-49 in Mice Transgenic for Its Ligand
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Medientyp:
E-Artikel
Titel:
Altered Phenotype and Function of Natural Killer Cells Expressing the Major Histocompatibility Complex Receptor Ly-49 in Mice Transgenic for Its Ligand
Beteiligte:
Olsson, Mats Y.;
Karre, Klas;
Sentman, Charles L.
Erschienen:
National Academy of Sciences of the United States of America, 1995
Erschienen in:Proceedings of the National Academy of Sciences of the United States of America
Sprache:
Englisch
ISSN:
0027-8424
Entstehung:
Anmerkungen:
Beschreibung:
<p>The Ly-49 molecule has been shown to interact with major histocompatibility complex (MHC) class I molecules, and the lytic function of Ly-49<sup>+</sup>natural killer (NK) cells from C57BL/6 (H-2<sup>b</sup>) mice is inhibited by the recognition of H-2D<sup>d</sup>on tumor target cells. Introduction of a Ly-49 ligand, H-2D<sup>d</sup>, into C57BL/6 mice did not alter the percentage of Ly-49<sup>+</sup>NK cells (13-18%), but it led to three functional effects on this subset. (i) The Ly-49 expression in the positive population was reduced by 30-50% compared to C57BL/6 control mice. (ii) While this Ly-49<sup>+</sup>subset (Ly-49lo) in the transgenic mice failed to kill BALB/c concanavalin A (Con A) blasts, which have high H-2D<sup>d</sup>expression, it was capable of killing SP2/0 tumor cells, which have low H-2D<sup>d</sup>expression. Ly-49<sup>+</sup>NK cells (Ly-49hi) from nontransgenic mice failed to kill both of these H-2D<sup>d</sup>-expressing target cells. (iii) In the transgenic mice, the Ly-49<sup>+</sup>subset acquired the ability to kill C57BL/6 Con A blasts, in contrast to the Ly-49<sup>+</sup>NK cells of C57BL/6 mice. We propose a "receptor-calibration" hypothesis, where low receptor density on the effector cells imposed by selection or adaptation to the environment allows higher sensitivity for detection of reduced self-MHC ligands on potential target cells.</p>