title: Ly49I NK cell receptor transgene inhibition of rejection of H2b mouse bone marrow transplants.
abstract: The Ly49 family of genes encode NK cell receptors that bind class I MHC Ags and transmit negative signals if the cytoplasmic domains have immunoregulatory tyrosine-based inhibitory motifs (ITIMs). 5E6 mAbs recognize Ly49C and Ly49I receptors and depletion of 5E6+ NK cells prevents rejection of allogeneic or parental-strain H2d bone marrow cell (BMC) grafts. To determine the function of the Ly49I gene in the rejection of BMC grafts, we transfected fertilized eggs of FVB mice with a vector containing DNA for B6 strain Ly49I (Ly49IB6). Ly49IB6 is ITIM+ and is recognized by 5E6 as well as Ly49I-specific 8H7 mAbs. Normal FVB H2q mice reject H2b but not H2d BMC allografts, and the rejection of H2b BMC was inhibited partially by anti-NK1.1 and completely by anti-asialo GM1, but not by anti-CD8, Abs. In FVB mice, NK1.1 is expressed on only 60% NK cells. FVB. Ly49IB6 hosts failed to reject H2d or H2b BMC, but did reject class I-deficient TAP-1-/- BMC, indicating that NK cells were functional. Nondepleting doses of anti-Ly49I Abs reversed the acceptance of H2b BMC by FVB.Ly49IB6 mice. FVB.Ly49IB6+/- mice were crossed and back-crossed with 129 mice-H2b, 5E6-, poor responders to H2d BMC grafts. While transgene-negative H2b/q F1 or first-generation back-crossed mice rejected H2b marrow grafts (hybrid resistance), transgene-positive mice did not. Thus B6 strain Ly49I receptors transmit inhibitory signals from H2b MHC class I molecules. Moreover, Ly49IB6 has no positive influence on the rejection of H2d allografts.
authors.affiliation: Department of Pathology, Laboratory of Molecular Pathology, Graduate Program in Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA.
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: M A
authors.initials: MA
authors.lastname: Morris
authors.forename: P
authors.initials: P
authors.lastname: Nguyen
authors.forename: T C
authors.initials: TC
authors.lastname: George
authors.forename: E
authors.initials: E
authors.lastname: Koulich
authors.forename: W C
authors.initials: WC
authors.lastname: Lai
authors.forename: J D
authors.initials: JD
authors.lastname: Schatzle
authors.forename: V
authors.initials: V
authors.lastname: Kumar
authors.forename: M
authors.initials: M
authors.lastname: Bennett
mesh_terms: D000818:Animals; D000950:Antigens, Ly; D016026:Bone Marrow Transplantation / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D003433:Crosses, Genetic; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D006084:Graft Rejection / Q000235:genetics* / Q000276:immunology*; D006085:Graft Survival / Q000235:genetics / Q000276:immunology; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008822:Mice, Transgenic; D055650:NK Cell Lectin-Like Receptor Subfamily A; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000235:genetics*; D055630:Receptors, NK Cell Lectin-Like; D019076:Transgenes / Q000276:immunology*
chemical_list: D000950:Antigens, Ly; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; C527091:Klra3 protein, mouse; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D055650:NK Cell Lectin-Like Receptor Subfamily A; D011971:Receptors, Immunologic; D055630:Receptors, NK Cell Lectin-Like