The nature of hemopoietic histocompatibility determinants. Differential sensitivity of Hh-1b and H-2b determinants to tunicamycin.
NK cell-dependent resistance of F1 hybrid mice to parental H-2b hemopoietic allografts is directed to cell surface structures controlled by the Hh-1 locus in or near the H-2D region. Crucial to an understanding of this enigmatic phenomenon is the information on the biochemical nature of the Hh-1 locus-controlled structures. Therefore, we examined the effect of tunicamycin (TM), an inhibitor of asparagine-linked glycosylation and ganglioside biosynthesis, on the expression of Hh-1 determinants in H-2b/Hh-1b lymphomas. The Hh-1b determinants on EL-4 and RBL-5 cells were no longer detectable after TM treatment, as demonstrated by the failure of the treated cells to inhibit hybrid resistance to parental H-2b bone marrow cells in vivo. This interpretation was supported by the unaltered ability of the TM-treated cells to localize in the spleens of irradiated F1 hybrid recipients. In contrast, TM caused only moderate reduction in H-2Kb and H-2Db expression as measured by binding of specific antibodies. This was accompanied by reduced susceptibility to alloimmune anti-H-2Db CTL, but not to anti-H-2Kb CTL. No decrease was found in the susceptibility to NK cell cytotoxicity in vitro. These data indicate that N-linked glycosylation or ganglioside synthesis is crucial for the expression of the Hh-1 locus-controlled target structures, but not for the H-2 class I molecules. The data also show that the Hh-1b determinants are substantially different from those which confer the susceptibility to NK cell-mediated in vitro cytotoxicity.
Milisauskas
V K
VK
Department of Pathology, School of Medicine, State University of New York, Buffalo 14214.
Nakamura
I
I
D000818:Animals; D016026:Bone Marrow Transplantation; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000032:analysis*; D005260:Female; D008040:Genetic Linkage; D006031:Glycosylation; D006183:H-2 Antigens / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000276:immunology; D008223:Lymphoma / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D014415:Tunicamycin / Q000494:pharmacology*
D000939:Epitopes; D006183:H-2 Antigens; D014415:Tunicamycin