TY - JOUR
T1 - Cre recombinase-mediated inactivation of H-2Dd transgene expression
T2 - Evidence for partial missing self-recognition by Ly49A NK cells
AU - Ioannidis, V.
AU - Zimmer, J.
AU - Beermann, F.
AU - Held, W.
PY - 2001/12/1
Y1 - 2001/12/1
N2 - We have established H-2Dd-transgenic (Tg) mice, in which H-2Dd 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-2Dd Tg in H-2b mice and acquired reactivity to cells lacking H-2Dd, both in vivo and in vitro. H-2Dd-Tg mice crossed to mice harboring an Mx-Cre Tg resulted in mosaic H-2Dd expression. That abrogated NK cell reactivity to cells lacking Dd. In Dd single Tg mice it is the Ly49A+ NK cell subset that reacts to cells lacking Dd, because the inhibitory Ly49A receptor is no longer engaged by its Dd ligand. In contrast, Ly49A+ NK cells from Dd × MxCre double Tg mice were unable to react to Dd-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 Dd expression thus impacts specifically missing Dd but not globally missing class I reactivity by Ly49A + NK cells. We propose that the absence of Dd from some host cells results in the acquisition of only partial missing self-reactivity.
AB - We have established H-2Dd-transgenic (Tg) mice, in which H-2Dd 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-2Dd Tg in H-2b mice and acquired reactivity to cells lacking H-2Dd, both in vivo and in vitro. H-2Dd-Tg mice crossed to mice harboring an Mx-Cre Tg resulted in mosaic H-2Dd expression. That abrogated NK cell reactivity to cells lacking Dd. In Dd single Tg mice it is the Ly49A+ NK cell subset that reacts to cells lacking Dd, because the inhibitory Ly49A receptor is no longer engaged by its Dd ligand. In contrast, Ly49A+ NK cells from Dd × MxCre double Tg mice were unable to react to Dd-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 Dd expression thus impacts specifically missing Dd but not globally missing class I reactivity by Ly49A + NK cells. We propose that the absence of Dd from some host cells results in the acquisition of only partial missing self-reactivity.
UR - http://www.scopus.com/inward/record.url?scp=0035575730&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.167.11.6256
DO - 10.4049/jimmunol.167.11.6256
M3 - Article
C2 - 11714788
AN - SCOPUS:0035575730
SN - 0022-1767
VL - 167
SP - 6256
EP - 6262
JO - Journal of Immunology
JF - Journal of Immunology
IS - 11
ER -