MHC-I antigen expression determines sensitivity of hematopoetic progenitor cells as targets for NK cells

Hybrid resistance is suggested to be mediated by NK lymphocytes as effector cells. NK cytotoxicity is triggered by specific NK cells receptors. One group of receptors recognizing MHC-I antigens is predominantly transmitting an inhibitory signal into the cell. However, NK cells have not been shown to recognize hematopoetic progenitor cells directly. In these studies we demonstrate that hematopoetic progenitor cells are sensitive targets for NK recognition. NK cytotoxicity is shown to depend on MHC-I antigen expression on these target cells. Bone marrow-derived hematopoetic progenitor cells from a beta 2-microglobulin-deficient mouse strain exhibit a significant increase of cytotoxic susceptibility compared with the wild type control. CFU-assays reveal an almost complete loss of proliferation after coincubating MHC-I-deficient bone marrow cells with NK cells from the wildtype mouse strain. The examination of H-2K in allorecognition of hematopoetic progenitor cells reveals an increased cytotoxicity after treatment of resistant syngeneic hematopoetic progenitor cells with H-2Kb F(ab)2-antibodies. Also masking of allogeneic hematopoetic progenitor cells with anti-H-2Kd F (ab)2-antibodies results in enhanced NK killing. Thus, hematopoetic progenitor cells are sensitive targets for NK cells and MHC-I antigen complex is the critical structure in NK recognition of hematopoetic progenitor cells. This complex mediates resistance of NK-specific lysis of hematopoetic progenitor cells.