Fetal and neonatal NK1.1⁺ Ly‐49⁻ cells can distinguish between major histocompatibility complex class Ihi and class Ilo target cells: Evidence for a Ly‐49‐independent negative signaling receptor

Natural killer (NK) cell function is regulated by both positive and negative signaling receptors. In adult splenic NK cells, negative signaling 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 expression of Ly-49 molecules is first detected on splenic NK1.1+ cells 4-6 days after birth. Despite the absence of these negative signaling receptors, fetal and neonatal Ly-49- NK cells lyse TAP-/- , major histocompatibility complex (MHC) class I(lo) but not TAP+/+, MHC class I(hi) target cells. This suggests that fetal and neonatal NK cells express negative signaling receptors other than Ly-49 molecules.