NATURAL-KILLER-CELLS RECOGNIZE COMMON ANTIGENIC MOTIFS SHARED BY H-2D(D), H-2L(D) AND POSSIBLY H-2D(R) MOLECULES EXPRESSED ON BONE-MARROW CELLS

Murine natural killer (NK) cells can mediate specific rejection of bone marrow cell (BMC) allografts. Whereas positive recognition of allogeneic MHC antigens forms the basis for T cell alloreactivity, it has been postulated that NK cells are reactive against targets that do not express certain self-encoded MHC class I antigens. Here, we study the immunogenicity of BMC grafts from two class I transgenic mice, D8 (B6 mice with an H-2D(d) transgene) and C3H.L(d) (C3H mice with an H-2L(d) transgene). D8 BMC grafts are acutely rejected by B6 but not D8 recipients. This suggests that antigenic motifs associated with the H-2D(d) molecule are recognized. B6 mice depleted of their CD3(+) but not NK1.1(+) cells can still reject D8 BMC grafts. These data suggest that NK1.1(+)/CD3(-) cells recognize the H-2D(d) derived antigenic motifs. Similarly, C3H.L(d) BMC grafts are rejected by B6 x C3H F-1 but not B6 x C3H.L(d) F-1 recipients. Thus, antigenic motifs associated with the H-2L(d) molecule can also be recognized. Furthermore, expression of either H-2D(d) or H-2L(d) by the recipients renders them unable to reject D8 or C3H.L(d) BMC grafts. Therefore, H-2D(d) and H-2L(d) molecules appear to express common antigenic motifs recognized by NK cells. Additional studies with B6.R4 ((KISDr)-I-b-S-b-D-b), an intra-H-2 recombinant mouse, indicated that a third class I molecule, possibly H-2D(r), also shared the common antigenic motifs with both H-2D(d) and H-2L(d) molecules. Thus, positive recognition of class I antigens by NK cells can occur. However, expression of some of these antigenic motifs appear to be negatively controlled by certain H-2(r) genes as suggested by rejection of D8 and B6.R4 BMC grafts by D8 x B10.RIII F-1 and B6.R4 x B10.RIII F-1 hybrids respectively.