Cloning of minimally divergent allelic forms of the natural killer (NK) receptor Ly-49C, differentially controlled by host genes in the MHC and 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/Sn (A) and C57BL/6 (B) origin. Analysis of AXB recombinant inbred strains suggested two loci regulating the expression, one segregating with the NK gene complex and the other with the MHC. In MHC congenic strains, the A form of Ly-49C had a low expression level and was further down-regulated in the presence of the H-2b haplotype (very low). The B form of Ly-49C had a high expression level and was down-regulated in the presence of H-2Kk (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 were cloned by reverse-transcriptase PCR from A/Sn and C57BL/6 mouse strains. The Ly-49C sequences from the two strains differed by six nucleotides leading to four predicted amino acid changes. Both cDNAs could be detected by the Ly-49C-specific Ab when expressed in EL-4 cells. Thus, like Ly-49A, Ly-49C expression is regulated by MHC class I molecules. Furthermore, A/Sn and C57BL/6 mice express different forms of Ly-49C that are down-regulated by different MHC class I molecules.
Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden.
J
J
Sundbäck
K
K
Kärre
C L
CL
Sentman
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D000950:Antigens, Ly; D003001:Cloning, Molecular; D003433:Crosses, Genetic; D018076:DNA, Complementary / Q000235:genetics; D005786:Gene Expression Regulation; D005796:Genes; D006183:H-2 Antigens / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D007694:Killer Cells, Natural / Q000378:metabolism*; D037181:Lectins, C-Type; D008285:Major Histocompatibility Complex / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics*; D008969:Molecular Sequence Data; D055630:Receptors, NK Cell Lectin-Like; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014162:Transfection
D000950:Antigens, Ly; D018076:DNA, Complementary; D006183:H-2 Antigens; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D055630:Receptors, NK Cell Lectin-Like; D011993:Recombinant Fusion Proteins