The role of Ly49A and 5E6(Ly49C) molecules in hybrid resistance mediated by murine natural killer cells against normal T cell blasts

We address the mechanism of hybrid resistance (HR) in vitro using NK effector cells and target lymphoblasts from H-2(b), H-2(d), and H-2(b/d) mice. The 5E6 (Ly49C)(+) subset of F1 NK cells lyse BALB/c (H-2(d)) but not B6 (H-2(b)) targets unless either anti-5E6 or anti-H-2K(b) MAbs are present. H-2D(d) transgenic B6 (D8) targets are not susceptible to F1 Ly49A(+) effecters. Furthermore, 5E6(+) Ly49A(+) F1 effecters lyse B6 and BALB/c targets only in the presence of anti-5E6 and anti-Ly49A MAbs, respectively. Thus, recognition of H-2K(b) by 5E6 and H-2D(d) by Ly49A transduce independent inhibitory signals. Moreover, anti-5E6 MAbs enable 5E6(+) BALB/c NK cells to lyse (BALB/c x B6)F1 targets. These data support the ''missing self'' and not the ''hemopoietic histocompatibility antigen'' hypothesis for HR. In addition, 5E6(+) NK cells from BALB/c and BALB.B, but not B6 or (BALB/c x B6)F1, mice receive negative signals from both H-2(d) and K-b class I antigens. Thus, allelic differences in 5E6 (C57BL versus BALB) may regulate recognition events by NK cells.