Natural killer cells recognize common antigenic motifs shared by H-2Dd, H-2Ld and possibly H-2Dr molecules expressed...

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-2Dd transgene) and C3H.Ld (C3H mice with an H-2Ld transgene). D8 BMC grafts are acutely rejected by B6 but not D8 recipients. This suggests that antigenic motifs associated with the H-2Dd 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-2Dd derived antigenic motifs. Similarly, C3H.Ld BMC grafts are rejected by B6 x C3H F1 but not B6 x C3H.Ld F1 recipients. Thus, antigenic motifs associated with the H-2Ld molecule can also be recognized. Furthermore, expression of either H-2Dd or H-2Ld by the recipients renders them unable to reject D8 or C3H.Ld BMC grafts. Therefore, H-2Dd and H-2Ld molecules appear to express common antigenic motifs recognized by NK cells. Additional studies with B6.R4 (KbIbSbDr), an intra-H-2 recombinant mouse, indicated that a third class I molecule, possibly H-2Dr, also shared the common antigenic motifs with both H-2Dd and H-2Ld 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-2r genes as suggested by rejection of D8 and B6.R4 BMC grafts by D8 x B10.RIII F1 and B6.R4 x B10.RIII F1 hybrids respectively.