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Publication : Cre recombinase-mediated inactivation of H-2Dd transgene expression: evidence for partial missing self-recognition by Ly49A NK cells.

First Author  Ioannidis V Year  2001
Journal  J Immunol Volume  167
Issue  11 Pages  6256-62
PubMed ID  11714788 Mgi Jnum  J:72831
Mgi Id  MGI:2153665 Doi  10.4049/jimmunol.167.11.6256
Citation  Ioannidis V, et al. (2001) Cre Recombinase-Mediated Inactivation of H-2D(d) Transgene Expression: Evidence for Partial Missing Self-Recognition by Ly49A NK Cells. J Immunol 167(11):6256-62
abstractText  We have established H-2D(d)-transgenic (Tg) mice, in which H-2D(d) expression can be extinguished by Cre recombinase-mediated deletion of an essential portion of the transgene (Tg). NK cells adapted to the expression of the H-2D(d) Tg in H-2(b) mice and acquired reactivity to cells lacking H-2D(d), both in vivo and in vitro. H-2D(d)-Tg mice crossed to mice harboring an Mx-Cre Tg resulted in mosaic H-2D(d) expression. That abrogated NK cell reactivity to cells lacking D(d). In D(d) single Tg mice it is the Ly49A(+) NK cell subset that reacts to cells lacking D(d), because the inhibitory Ly49A receptor is no longer engaged by its D(d) ligand. In contrast, Ly49A(+) NK cells from D(d) x MxCre double Tg mice were unable to react to D(d)-negative cells. These Ly49A(+) NK cells retained reactivity to target cells that were completely devoid of MHC class I molecules, suggesting that they were not anergic. Variegated D(d) expression thus impacts specifically missing D(d) but not globally missing class I reactivity by Ly49A(+) NK cells. We propose that the absence of D(d) from some host cells results in the acquisition of only partial missing self-reactivity.
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