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 aliogeneic 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 Immunogenlclty of BMC grafts from two class I transgenlc 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 × C3H F₁ but not B6 × C3H.L^d F₁ 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 (K^bI^bS^bD^r), 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 × B10.RIII F_d and B6.R4 × B10.RIII F₁ hybrids respectively.