cDNA cloning of mouse NKR-P1 and genetic linkage with LY-49. Identification of a natural killer cell gene complex on mouse chromosome 6.
NK cells lyse tumor cells and virally infected cells, but the molecular basis for this phenomenon has not been defined. A mAb specific for the rat cell surface molecule, NKR-P1, stimulates rat NK cell lytic activity and is reactive with all rat NK cells, suggesting that this molecule may play a significant role in NK cell function. We have previously described another NK cell-specific Ag, Ly-49, that belongs to a family of cross-hybridizing genes on distal mouse chromosome 6. The rat NKR-P1 Ag shares several features with the mouse Ly-49 Ag, including selective cell surface expression on NK cells, homology to the C-type lectins, expression as a type II integral membrane protein, and disulfide-linked homodimeric structure. To further examine the relationship of NKR-P1 to Ly-49, we have cloned the cDNA encoding a mouse homologue of NKR-P1 (mNKR-P1). The mouse and rat NKR-P1-deduced polypeptide sequences are highly conserved, suggesting a similar tertiary structure. By examination of DNA from informative recombinant inbred mice with Southern blot analysis, we have determined that mNKR-P1 is encoded by a distinct gene that is genetically linked to the Ly-49 locus, lying within 0.5 centi-Morgan (cM) of Ly-49. Although the deduced amino acid sequences of mNKR-P1 and Ly-49 reveal that these proteins are structurally similar, they are only 24% identical at the amino acid level and the cDNA sequences do not demonstrate significant nucleotide homology. Our studies suggest that we have identified a region on mouse chromosome 6 that includes distinct NK-specific genes that encode structurally related proteins (type II integral membrane proteins, C-type lectin super-gene family) but which demonstrate considerable heterogeneity. We have termed this genetic region the NK complex.
Rosalind Russell Arthritis Research Laboratory, Department of Medicine, University of California, San Francisco 94143.
W M
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Yokoyama
J C
JC
Ryan
J J
JJ
Hunter
H R
HR
Smith
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Stark
W E
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Seaman
D000595:Amino Acid Sequence; D000818:Animals; D000950:Antigens, Ly / Q000235:genetics*; D000954:Antigens, Surface / Q000235:genetics*; D037263:Asialoglycoprotein Receptor; D001483:Base Sequence; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D005796:Genes; D008040:Genetic Linkage; D007694:Killer Cells, Natural / Q000502:physiology*; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D055651:NK Cell Lectin-Like Receptor Subfamily B; D012150:Polymorphism, Restriction Fragment Length; D011971:Receptors, Immunologic / Q000235:genetics; D016415:Sequence Alignment
D000950:Antigens, Ly; D000954:Antigens, Surface; D037263:Asialoglycoprotein Receptor; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011971:Receptors, Immunologic; D004247:DNA