title: The ability of H-2Dd molecule to affect natural resistance to hemopoietic allografts is an intrinsic property shared by Ddm1 but not Ld.
abstract: F1 hybrid resistance (HR) to parental bone marrow grafts is mediated by natural killer (NK) cells, and thought to be controlled by the non-class I hemopoietic histocompatibility (Hh) genes linked to the major histocompatibility complex (MHC). However, as in the in vitro NK cytotoxicity against hemopoietic targets, expression of certain class I MHC molecules does affect HR, although mechanisms underlying such an effect are not understood. In this study, we examine the relevance of the "self/non-self" property of class I molecules and the molecular domains responsible for this function. H-2b/Hh-1b lymphoma cells were transfected with class I H-2Dd or Ld gene, and its effect on the Hh-1 phenotype was examined by testing the transfectant's ability to competitively inhibit the in vivo rejection of parental H-2b/Hh-1b bone marrow grafts by irradiated F1 hybrid hosts. Multiple independent clones of transfectants show that the genomic or cDNA of the Dd gene, but not of Ld, renders the Hh-1b-positive cells incapable of inhibiting HR in F1 mice, although both genes belong to the same region of the same haplotype. The same effect could be observed not only in H-2b/d F1 mice for which Dd and Ld are self, but also in H-2b/k F1 mice for which both Dd and Ld are non-self. Thus, this function of the Dd molecule is an intrinsic property, not necessarily related to its self/non-self characteristic relative to the effector cells. Furthermore, given the nature of the assay used in this study, the results favor a "target interference" model as the underlying mechanism of the Dd effect. To locate the relevant domain(s) of the Dd molecule, mutant Ddm1 gene was tested and found to have the same effect as the non-mutant Dd. Ddm1 is a hybrid molecule between Dd and Ld, sharing with Dd only the alpha 1 domain and a portion of the alpha 2 domain. The two N-terminal domains of Ddm1 differ from those of Dd by three amino acid substitutions, two of which affect the molecules' peptide-binding properties.
authors.affiliation: Department of Pathology, SUNY at Buffalo 14214.
authors.forename: V K
authors.initials: VK
authors.lastname: Milisauskas
authors.forename: I
authors.initials: I
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D006183:H-2 Antigens / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D017710:Lymphocyte Transfusion; D008214:Lymphocytes / Q000276:immunology*; D008223:Lymphoma / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D014162:Transfection
chemical_list: D006183:H-2 Antigens