Heterogeneity Among Ly-49C Natural Killer (NK) Cells: Characterization of Highly Related Receptors with Differing Functions and Expression Patterns

Ly-49C is a member of the polymorphic family of murine NK cell inhibitory receptors. The 5E6 antibody that defines a subset of NK cells responsible for the rejection of parental H-2(d) bone marrow by F(1) mice has been shown previously to react with Ly-49C. Here, the 5E6 antibody was found to detect two Ly-49C-related molecules in B6 mice. Two cDNA clones were isolated from B6 NK cells, one identical to previously reported Ly-49C(B6) and the other a novel cDNA. The deduced amino acid sequence of the latter differs from that of Ly-49C(BALB) at only 4 residues, 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 another anti-Ly-49C antibody, 4LO3311, binds to the newly described Ly-49C but not the previously reported Ly-49C(B6). Two-color flow cytometric analysis detected 5E6(+)4LO3311(−) as well as 5E6(+)4LO3311(+) subsets of NK cells from B6, but not BALB/c, mice. The level of Ly-49C expression 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 results demonstrate that the newly described Ly-49C(B6), not the previously reported Ly-49C(B6), is the probable B6 allelic form of Ly49C. The previously reported Ly-49C(B6) must be encoded by a separate gene and should be renamed Ly-49I. The implication of these results with respect to the role of Ly-49C in hybrid resistance is discussed.