INHIBITION OF NATURAL-KILLER CELL-MEDIATED BONE-MARROW GRAFT-REJECTION BY ALLOGENEIC MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I, BUT NOT CLASS-II MOLECULES

The role of major histocompatibility complex (MHC) class I and class II molecules in natural killer (NK) cell-mediated rejection of allogeneic, semi-syngeneic and MHC-matched bone marrow grafts was investigated. The use of beta(2)-microglobuln (beta(2)m) -/- and beta(2)m +/- mice as bone marrow donors to MHC-mismatched recipients allowed an analysis of whether the presence of semi-syngeneic and allogeneic MHC class I gene products would be triggering, protective or neutral, in relation to NK cell-mediated rejection. Loss of beta(2)m did not allow H-2(b) bone marrow cells to escape from NK cell-mediated rejection in allogeneic (BALB/c) or semi-allogeneic (H-2D(d) transgenic C57BL/6) mice. On the contrary, it led to stronger rejection, as reflected by the inability of a larger bone marrow cell inoculum to overcome rejection by the H-2-mismatched recipients. In H-2-matched recipients, loss of beta(2)m in the graft led to a switch from engraftment to rejection. At the recipient level, loss of beta(2)m led to loss of the capability to reject H-2-matched beta(2)m-deficient as well as allogeneic grafts. When MHC class II-deficient mice were used as donors, the response was the same as that against donors of normal MHC phenotype: allogeneic and semi-syngeneic grafts were rejected by NK cells,while syngeneic grafts were accepted. These data suggest a model in which allogeneic class I molecules on the target cell offer partial protection, while certain syngeneic class I molecules give full protection from NK cell-mediated rejection of bone marrow cells. There was no evidence for a role of MHC class II molecules in this system.