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Publication : A "chimeric" C57l-derived Ly49 inhibitory receptor resembling the Ly49D activation receptor.

First Author  Mehta IK Year  2001
Journal  Cell Immunol Volume  209
Issue  1 Pages  29-41
PubMed ID  11414734 Mgi Jnum  J:70159
Mgi Id  MGI:2136518 Doi  10.1006/cimm.2001.1786
Citation  Mehta IK, et al. (2001) A 'chimeric' C57l-derived Ly49 inhibitory receptor resembling the Ly49D activation receptor. Cell Immunol 209(1):29-41
abstractText  Ly49D is a natural killer (NK) cell activation receptor that is responsible for differential mouse inbred strain-determined lysis of Chinese hamster ovary (CHO) cells. Whereas C57BL/6 NK cells kill CHO, BALB/c-derived NK cells cannot kill because they lack expression of Ly49D. Furthermore, the expression of Ly49D, as detected by monoclonal antibody 4E4, correlates well with CHO lysis by NK cells from different inbred strains. However, one discordant mouse strain was identified; C57L NK cells express the mAb 4E4 epitope but fail to lyse CHO cells. Herein we describe a Ly49 molecule isolated from C57L mice that is recognized by mAb 4E4 (anti-Ly49D). Interestingly, this molecule shares extensive similarity to Ly49D(B6) in its extracellular domain, but its cytoplasmic and transmembrane domains are identical to the inhibitory receptor Ly49A(B6), including a cytoplasmic ITIM. This molecule bears substantial overall homology to the previously cloned Ly49O molecule from 129 mice the serologic reactivity and function of which were undefined. Cytotoxicity experiments revealed that 4E4(+) LAK cells from C57L mice failed to lyse CHO cells and inhibited NK cell function in redirected inhibition assays. MHC class I tetramer staining revealed that the Ly49O(C57L)-bound H-2D(d) and lysis by 4E4(+) C57L LAK cells is inhibited by target H-2D(d). The structural basis for ligand binding was also examined in the context of the recent crystallization of a Ly49A-H-2D(d) complex. Therefore, this apparently 'chimeric' Ly49 molecule serologically resembles an NK cell activation receptor but functions as an inhibitory receptor. Copyright 2001 Academic Press.
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