Identification of a human member of the Ly-49 multigene family.
Three classes of multigene family-encoded receptors enable NK cells to discriminate between polymorphic MHC class I molecules: Ly-49 homodimers, CD94/NKG2 heterodimers and the killer cell inhibitory receptors (KIR). Of these, CD94/NKG2 has been characterized in both rodents and humans. In contrast, Ly-49 family members have hitherto been found only in rodents, and KIR molecules only in the human. In this report, we describe a human cDNA, termed Ly-49L, that constitutes the first human member of the Ly-49 multi-gene family. Compared with rodent Ly-49 molecules, the Ly-49L sequence contains a premature stop codon and predicts a truncated protein that lacks the distal part of a C-terminal lectin domain. Evidence is presented that the premature stop codon results from incomplete excision of the intron between the first two lectin domain exons. Splice variants predicting a full-size Ly-49L protein were not detected. As demonstrated by Northern blot analysis, Ly-49L was transcribed by IL-2-activated NK cells, but not by freshly isolated B or T cells. PCR screening of a 22-clone yeast artificial chromosome contig localized the LY49L locus to the human NK gene complex on chromosome 12p12-p13. Southern blot analysis of genomic DNA showed a simple pattern with a full-length Ly-49L probe at low stringency hybridization conditions, suggesting that Ly-49L may be the only human member of the Ly-49 multigene family.
Westgaard
I H
IH
Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, Norway. i.h.westgaard@basalmed.uio.no
Berg
S F
SF
Orstavik
S
S
Fossum
S
S
Dissen
E
E
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D000950:Antigens, Ly / Q000145:classification / Q000235:genetics*; D001483:Base Sequence; D002874:Chromosome Mapping; D018076:DNA, Complementary; D005091:Exons; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D051381:Rats; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic
D000950:Antigens, Ly; D018076:DNA, Complementary