FETAL AND NEONATAL NK1.1(-49(-) CELLS CAN DISTINGUISH BETWEEN MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I-HI AND CLASS I-LO TARGET-CELLS - EVIDENCE FOR A LY-49-INDEPENDENT NEGATIVE SIGNALING RECEPTOR() LY)

Natural killer (NK) cell function is regulated by both positive and ne gative signaling receptors. In adult splenic NK cells, negative signal ing has been shown to be mediated by the Ly-49 family receptors. NK1.1 (+)2B4(+)CD3(-) cells that are phenotypically and functionally similar to adult splenic NK cells can be derived from murine fetal liver and thymus. These cells do not express any known Ly-49 molecules on their surface nor do they contain the known Ly-49 transcripts. Surface expre ssion of Ly-49 molecules is first detected on splenic NK1.1(+) cells 4 -6 days after birth. Despite the absence of these negative signaling r eceptors, fetal and neonatal Ly-49(-) NK cells lyse TAP(-/-), major hi stocompatibility complex (MHC) class I-lo but not TAP(+/+), MHC class I-hi target cells. This suggests that fetal and neonatal NK cells expr ess negative signaling receptors other than Ly-49 molecules.