Allelic variation in the ectodomain of the inhibitory Ly-49G2 receptor alters its specificity for allogeneic and xenogeneic ligands.
The Ly-49 multigene receptor family regulates mouse NK cell functions. A number of Ly-49 genes exhibit allelic variation, but the functional significance of allelic differences in extracellular domains of Ly-49 receptors regarding ligand specificity is largely unknown. Amino acid differences exist in the extracellular domains of the B6 and BALB/c allele products of the inhibitory Ly-49G receptor. We constructed chimeric Ly-49 receptors consisting of common cytoplasmic and transmembrane regions of the activating Ly-49W receptor fused with the ectodomains of the B6 and BALB/c alleles of Ly-49G. Expression of these chimeras in the RNK-16 rat NK cell line allowed us to study the specificity of inhibitory receptor ectodomains as they stimulated NK lytic activity. We found that the ectodomain of the BALB/c allele of Ly-49G recognizes both H-2D(d) and D(k) class I MHC alleles, whereas the ectodomain of the B6 allele of Ly-49G recognizes D(d), and not D(k). The specificity for D(k) as well as D(d) of the wild-type Ly-49G(BALB/c) allele product was confirmed with RNK-16 transfectants of this inhibitory receptor. Furthermore, the ectodomain of the Ly-49G(BALB/c) allele recognizes a distinct repertoire of xenogeneic ligands that only partially overlaps with that recognized by Ly-49G(B6). Our results indicate that allelic variation in Ly-49 extracellular domains can have functional significance by altering Ly-49 receptor specificity for mouse class I MHC and xenogeneic ligands.
Silver
Elizabeth T
ET
Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Canada.
Lavender
Kerry J
KJ
Gong
Dong-Er
DE
Hazes
Bart
B
Kane
Kevin P
KP
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D015478:Antigens, Heterophile / Q000378:metabolism*; D000950:Antigens, Ly / Q000378:metabolism*; D016466:CHO Cells; D006224:Cricetinae; D003602:Cytotoxicity, Immunologic / Q000235:genetics*; D005110:Extracellular Space / Q000235:genetics / Q000276:immunology; D005260:Female; D014644:Genetic Variation / Q000276:immunology*; D006183:H-2 Antigens / Q000378:metabolism; D007519:Isoantigens / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D037181:Lectins, C-Type; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D055630:Receptors, NK Cell Lectin-Like; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000138:chemical synthesis; D013045:Species Specificity; D014407:Tumor Cells, Cultured
D015478:Antigens, Heterophile; D000950:Antigens, Ly; D006183:H-2 Antigens; D007519:Isoantigens; D037181:Lectins, C-Type; D008024:Ligands; C452844:Ly49G2 receptor; D011971:Receptors, Immunologic; D055630:Receptors, NK Cell Lectin-Like; D011993:Recombinant Fusion Proteins