CLONING OF MINIMALLY DIVERGENT ALLELIC FORMS OF THE NATURAL-KILLER (NK) RECEPTOR LY-49C, DIFFERENTIALLY CONTROLLED BY HOST GENES IN THE MHCAND NK GENE COMPLEXES

We have investigated whether expression of Ly-49C, detected by the mAb SW5E6, is subject to similar regulation by host MHC as is Ly-49A. Ly- 49C expression was regulated by host MHC differentially in mice of A/S n (A) and C57BL/6 (B) origin, Analysis of AXE recombinant inbred strai ns suggested two loci regulating the expression, one segregating with the NK gene complex and the other with the MHC. In MHC congenic strain s, the A form of Ly-49C had a low expression level and was further dow nregulated in the presence of the H-2(b) haplotype (very low). The B f orm of Ly-49C had a high expression level and was down-regulated in th e presence of H-2K(k) (medium). To test the hypothesis that the Ly-49C receptor in A/Sn and C57BL/6 mice may be differentially regulated by MHC products because they represent allelic forms, cDNAs for Ly-49C we re cloned by reverse-transcriptase PCR from A/Sn and C57BL/6 mouse str ains, The Ly-49C sequences from the two strains differed by six nucleo tides leading to four predicted amino acid changes. Both cDNAs could b e detected by the Ly-49C-specific Ab when expressed in EL-4 cells. Thu s, like Ly-49A, Ly-49C expression is regulated by MHC class I molecule s. Furthermore, A/Sn and C57BL/6 mice express different forms of Ly-49 C that are down-regulated by different MHC class I molecules.