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, semisyngeneic and MHC-matched bone marrow grafts was investigated. The use of beta 2-microglobulin (beta 2m) -/- and beta 2m +/- 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 2m did not allow H-2b bone marrow cells to escape from NK cell-mediated rejection in allogeneic (BALB/c) or semi-allogeneic (H-2Dd 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 2m in the graft led to a switch from engraftment to rejection. At the recipient level, loss of beta 2m led to loss of the capability to reject H-2-matched beta 2m-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.
Ohlén
C
C
Microbiology and Tumor Biology Center (MTC), Karolinska Institute, Stockholm, Sweden.
Höglund
P
P
Sentman
C L
CL
Carbone
E
E
Ljunggren
H G
HG
Koller
B
B
Kärre
K
K
D000818:Animals; D017951:Antigen Presentation; D016026:Bone Marrow Transplantation; D006084:Graft Rejection / Q000276:immunology*; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D018448:Models, Immunological; D011828:Radiation Chimera / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic; D001613:beta 2-Microglobulin / Q000172:deficiency / Q000235:genetics
D006183:H-2 Antigens; C024755:H-2K(K) antigen; C032876:H-2Kb protein, mouse; D000949:Histocompatibility Antigens Class II; D001613:beta 2-Microglobulin