Ly49A allelic variation and MHC class I specificity.
The Ly49 family of natural killer (NK) cell receptors is encoded by a polygenic genetic locus. Allelic forms have been described and their expression appears to be regulated. The best-characterized Ly49 molecule, the C57BL/6 form of Ly49A, is an NK cell inhibitory receptor that binds H2Dd. To determine whether differences between Ly49a alleles may have functional consequences, allelic variants of Ly49a were cloned from several inbred mouse strains. Stable transfectants expressing each Ly49a allelic variant were generated and tested for reactivity with a panel of monoclonal antibodies (mAbs A1, JR9.318, YE1/32, and YE1/48) that recognize the C57BL/6 form of Ly49A. Binding to H2Dd was also assessed using fluorescently labeled H2Dd tetramers. Furthermore, cytotoxicity assays were performed using anti-Ly49A mAb-separated interleukin-2-activated NK cells. We show that despite binding to fluorescently labeled H2Dd tetramers, the Ly49A+ NK cells from representative mouse strains displayed significantly different degrees of inhibition with H2Dd targets. These results can be interpreted in the light of recent structural data on the Ly49A-H2Dd complex. Thus, the Ly49 family displays functionally significant allelic polymorphism which adds to the repertoire of NK cell receptors.
Mehta
I K
IK
Department of Medicine, Center for Arthritis and Related Diseases, Box 8045, Washington University School of Medicine and Howard Hughes Medical Institute, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Wang
J
J
Roland
J
J
Margulies
D H
DH
Yokoyama
W M
WM
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D000950:Antigens, Ly; D001483:Base Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics*; D003001:Cloning, Molecular; D003602:Cytotoxicity, Immunologic; D014644:Genetic Variation; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D037181:Lectins, C-Type; D016131:Lymphocyte Subsets / Q000276:immunology*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D008969:Molecular Sequence Data; D055650:NK Cell Lectin-Like Receptor Subfamily A; D011946:Receptors, Antigen / Q000276:immunology; D011971:Receptors, Immunologic / Q000737:chemistry / Q000235:genetics*; D055630:Receptors, NK Cell Lectin-Like; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity
D000950:Antigens, Ly; D002352:Carrier Proteins; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D015395:Histocompatibility Antigens Class I; C527088:Klra1 protein, mouse; D037181:Lectins, C-Type; D008565:Membrane Proteins; D055650:NK Cell Lectin-Like Receptor Subfamily A; D011946:Receptors, Antigen; D011971:Receptors, Immunologic; D055630:Receptors, NK Cell Lectin-Like