MURINE NK CELL ALLOSPECIFICITY-1 IS DEFINED BY INHIBITORY LIGANDS

Hemopoietic allografts of normal and neoplastic origin are subject to NK cell-mediated resistance in mice. Susceptibility to this resistance is controlled by MHC-linked genes in a recessive manner. Several dist inct specificities could be postulated to explain the strain-dependent pattern of resistance. These presumptive specificities for recognitio n are H-2 haplotype dependent, but the correspondence is not one-to-on e. For example, resistance of H-2(d) or H-2(b/d) host to H-2(b) graft operationally defines specificity-1, establishing its link with haplot ype H-2(b). To examine the molecular basis of specificity-1, spontaneo us D-d-loss mutant clones were isolated from H-2(b/d) and H-2(d) hemop oietic cell lines, i.e., 416B of (C57BL/6 x DBA/2)F-1 (B6D2F(1)) origi n and L1210 of DBA/2 origin, both of which lack specificity-1. The exp ression of specificity-1 in the mutant clones was examined in vivo and in vitro. The results indicate that D-d-loss clones of 416B and L1210 lines express specificity-1. These data suggest that murine NK cell a llospecificity-1 is defined primarily by the absence of the D-d molecu le or other class I molecules sharing the protective motifs; no H-2(b) -associated genes play a relevant role. This conclusion is consistent with the missing self hypothesis of NK cell reactivity, and is in agre ement with the observation that lysis of B6 targets by B6D2F(1) NK cel ls is mediated mostly by cells that express Ly-49A and/or Ly-49G2.