HETEROGENEITY AMONG LY-49C NATURAL-KILLER (NK) CELLS - CHARACTERIZATION OF HIGHLY RELATED RECEPTORS WITH DIFFERING FUNCTIONS AND EXPRESSIONPATTERNS

Ly-49C is a member of the polymorphic family of murine NK cell inhibit ory receptors. The 5E6 antibody that defines a subset of NK cells resp onsible for the rejection of parental H-2(d) bone marrow by Fl mice ha s been shown previously to react with Ly-49C. Here, the 5E6 antibody w as found to detect two Ly-49C-related molecules in B6 mice. Two cDNA c lones were isolated from B6 NK cells, one identical to previously repo rted Ly-49C(B6) and the other a novel cDNA. The deduced amino acid seq uence of the latter differs from that of Ly-49C(BALB) at only 4 residu es, whereas the previously reported Ly-49C(B6) differs at 22 residues. Flow cytometric analyses of COS cells transfected with the two cDNAs showed that the 5E6 antibody binds to both Ly-49 molecules, while anot her anti-Ly-49C antibody, 4LO3311, binds to the newly described Ly-49C but not the previously reported Ly-49C(B6). Two-color now cytometric analysis detected 5E6(+)4LO3311(-) as well as 5E6(+)4LO3311(+) subsets of NR cells from B6, but not BALB/c, mice. The level of Ly-49C expres sion on B6 NK cells detected by the 4LO3311 antibody was substantially lower than that on BALB/c NK cells. Binding specificity of the novel Ly-49C(B6) was indistinguishable from that of Ly-49C(BALB), whereas no binding was detectable with previously reported Ly-49C(B6). These res ults demonstrate that the newly described Ly-49C(B6), not the previous ly reported Ly-49C(B6), is the probable B6 allelic form of Ly-49C. The previously reported Ly-49C(B6) must be encoded by a separate gene and should be re named Ly-49I. The implication of these results with resp ect to the role of Ly-49C in hybrid resistance is discussed.