Expression of different members of the Ly-49 gene family defines distinct natural killer cell subsets and cell adhesion properties.
The murine Ly-49 antigen belongs to a family of type II transmembrane molecules containing lectin-like domains. The original member of this family, Ly-49A, has been demonstrated to be expressed by a subpopulation of natural killer (NK) cells, bind certain class I major histocompatibility complexes (MHC), and act as a negative regulator of lytic activity. The expression patterns and functional activities of the other Ly-49s, however, is unknown. We extended the study of this family by isolating cDNAs encoding two new Ly-49 molecules. The reactivity of these and previously identified Ly-49 molecules with NK antibodies was tested in a COS cell expression system. YE1/32 and YE1/48 bound Ly-49A specifically, and 5E6 reacted only with Ly-49C. Three-color flow cytometric analysis demonstrated Ly-49A and Ly-49C expression defines complex, but distinct subsets within NK1.1+ cells. Some NK1.1-CD3+ as well as NK1.1-CD3- cells expressing Ly-49A or C were also detected. Analysis of MHC congenic strains of mice demonstrated that YE1/32+ and YE1/48+ NK cells are not deleted, as has been shown with the Ly-49A mAb A1. Furthermore, COS cells transfected with Ly-49A bound H-2d and H-2k cell lines, whereas Ly-49C transfectants bound H-2d, H-2k, H-2b, and H-2s. The antibodies 5E6 and 34-1-2S (anti-class I MHC) inhibited the binding of Ly-49C to an H-2s cell line. These results imply that the NK cell antigens Ly-49A and C bind to different repertoires of class I MHC molecules.
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
J
J
Brennan
D
D
Mager
W
W
Jefferies
F
F
Takei
D000595:Amino Acid Sequence; D000818:Animals; D000950:Antigens, Ly; D000954:Antigens, Surface / Q000096:biosynthesis; D001483:Base Sequence; D002448:Cell Adhesion / Q000276:immunology*; D002460:Cell Line; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D016384:Consensus Sequence; D017931:DNA Primers; D018076:DNA, Complementary / Q000032:analysis; D015870:Gene Expression; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000502:physiology; D037181:Lectins, C-Type; D016131:Lymphocyte Subsets / Q000276:immunology* / Q000502:physiology; D008285:Major Histocompatibility Complex; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D005810:Multigene Family; D055650:NK Cell Lectin-Like Receptor Subfamily A; D016133:Polymerase Chain Reaction; D055630:Receptors, NK Cell Lectin-Like; D017386:Sequence Homology, Amino Acid; D013154:Spleen / Q000276:immunology; D014162:Transfection
D000950:Antigens, Ly; D000954:Antigens, Surface; D017931:DNA Primers; D018076:DNA, Complementary; C527088:Klra1 protein, mouse; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D055650:NK Cell Lectin-Like Receptor Subfamily A; D055630:Receptors, NK Cell Lectin-Like