Rejection of class I MHC-deficient haemopoietic cells by irradiated MHC-matched mice

Abstract

Irradiated MHC-heterozygous mice often reject bone marrow cells transplanted from one of the homozygous parental strains, a phenomenon ('hybrid resistance') that appears to violate the laws of transplantation. Rejection of parental and allogeneic marrow cells also differs from conventional T cell-mediated rejection mechanisms as it is effected by NK1.1+ cells. To account for the unusual specificity of bone marrow rejection, it has been proposed that NK1.1+ cells destroy marrow cells that fail to express the full complement of self MHC class I (MHC-I) molecules. We show here that NK1.1+ cells in normal mice reject haemopoietic transplants from mice that are deficient for normal cell-surface MHC-I expression because of a targeted mutation in the beta 2-microglobulin gene. These findings demonstrate that deficient expression of MHC-I molecules renders marrow cells susceptible to rejection.

In vivo tumor cell rejection induced by NK cell inhibitory receptor blockade: Maintained tolerance to normal cells even in the presence of IL‐2

“…Studies in mice demonstrated that NK cells vigorously reject both neoplastic and normal, healthy cells lacking one or more self MHC class I ligands [4,5,[21][22][23]. Adoptive transfer of activated NK cells with missing-self-reactivity against the host can reduce GVH disease, promote BM engraftment and provide graft-versustumor responses [24,25].…”

Distinct KIR/HLA compound genotypes affect the kinetics of human antiviral natural killer cell responses

“…For example, NK cells that express MHC class I-specific inhibitory receptors have been found to be functionally reactive, but NK cells that lack MHC class I-specific inhibitory receptors are hyporeactive to the same stimuli and do not exhibit cytotoxicity to MHC class I-deficient target cells (27,28). Likewise, inhibitory receptor-expressing NK cells of MHC class I-deficient patients (29)(30)(31) and NK cells of β 2 m -/- (32)(33)(34), TAP -/- (31,35), or MHC-deficient (34, 36) mice do not kill MHC class I-deficient normal cells.…”

Intrabody-mediated phenotypic knockout of major histocompatibility complex class I expression in human and monkey cell lines and in primary human keratinocytes

“…It has been demonstrated by other groups that NK cells recognize and lyse syngeneic lymphoblasts and bone marrow cells from ␤2-microglobulin Ϫ/Ϫ or TAP Ϫ/Ϫ donors. [71][72][73] In contrast, data from ␤2-microglobulin-deficient mice showed that skin grafts from those deficient mice were not recognized by NK cells. 64 The same may be true for the human immune system however, this still must be elucidated in vivo.…”