The nature of hemopoietic histocompatibility determinants: Differential sensitivity of Hh-1^b and H-2^b determinants to tunicamycin

NK cell-dependent resistance of F₁ hybrid mice to parental H-2^b 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-2^b/Hh-1^b lymphomas. The Hh-1^b 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-2^b 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-2K^b and H-2D^b expression as measured by binding of specific antibodies. This was accompanied by reduced susceptibility to alloimmune anti-H-2D^b CTL, but not to anti-H-2K^b 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-1^b determinants are substantially different from those which confer the susceptibility to NK cell-mediated in vitro cytotoxicity.