Hybrid resistance: 'negative' and 'positive' signaling of murine natural killer cells

Abstract

Murine NK cells can reject allogenic or parental-strain bone marrow cells (BMC) in vivo and can lyse T lymphoblasts in vitro. The 'missing self' hypothesis states that absence or presence of 'negative signals' from target cell class I antigens (Ag) to NK receptors determines whether or not lysis occurs. Indeed, lysis of parental-strain blasts by purified F1 NK cell subsets occurred only in the presence of anti-receptor antibodies. Evidence for 'positive signaling' to NK cells by class I Ag includes rejection of D8 (Dd) transgene to B6) BMC by B6 hosts. The outcome of other BMC transplants contradict the missing self idea, because donors with identical class I Ag differ in compatibility with certain hosts. Perhaps class I Ag-NK cell receptor interactions dominate over other target-NK cell interactions. These interactions are usually 'negative' but can be 'positive'.