Identification of the mouse killer immunoglobulin-like receptor-like (Kirl) gene family mapping to chromosome X.
Natural killer (NK) inhibitory receptors, which recognize major histocompatability complex (MHC) proteins in humans, are known as killer Ig-like receptors (KIRs) and are encoded by a multi-gene immunoglobulin (Ig) superfamily. In a screen for genes differentially expressed in the mouse thymus, we discovered the first close rodent homologue of the NK receptor KIR family, which we named KIR- Like (Kirl). KIRL1 shares 40% amino acid identity with primate KIR family members, with the majority of the homology contained within the Ig-like ectodomains. KIRL1 is more similar to the KIRs than to any other known member of the Ig domain-containing leukocyte receptor superfamily. This highly significant homology suggests that the KIR family did not arise independently in primates, as has been previously suggested, but rather evolved from a primordial gene already present in the common rodent/primate ancestor. KIRL1 lacks the cytoplasmic protein motifs that mediate inhibition in KIRs (immunoregulatory tyrosine inhibiting motif, ITIM); KIRL1 also lacks the transmembrane activation signature (a conserved K residue involved in association with the immunoregulatory tyrosine activating motif-containing DAP12 molecule) found in some KIRs. Nevertheless, we hypothesize that Kirl1 is functional, for the following reasons: (1) Kirl1 mRNA is expressed at high levels in immature thymocytes; (2) Kirl1 is regulated during thymocyte development; (3) KIRL1 protein is detected in thymus. We also show that the mouse genome contains a closely related, transcribed gene, which we name Kirl2. Kirl2 encodes a KIR-like molecule with three Ig-like domains and also lacks tyrosine-based immunoregulatory motifs in its cytoplasmic region.
Welch
Alice Y
AY
Immunology Department, Holland Laboratory for Biomedical Research, American Red Cross, 15601 Crabbs Branch Way, Rockville, MD 20855, USA.
Kasahara
Masanori
M
Spain
Lisa M
LM
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D008969:Molecular Sequence Data; D005810:Multigene Family; D010802:Phylogeny; D012313:RNA / Q000235:genetics; D011971:Receptors, Immunologic / Q000235:genetics* / Q000378:metabolism; D054340:Receptors, KIR; D054341:Receptors, KIR3DL1; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D014960:X Chromosome / Q000235:genetics*
D018076:DNA, Complementary; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054341:Receptors, KIR3DL1; D012313:RNA