Journal of Experimental Medicine, Vol 159, 1132-1148, Copyright © 1984 by Rockefeller University Press

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Natural resistance of lethally irradiated F1 hybrid mice to parental marrow grafts is a function of H-2/Hh-restricted effectors

JP Daley and I Nakamura

The natural resistance of F1 hybrid mice against parental bone marrow grafts is thought to be mediated by natural killer (NK)-like effector cells. However, unlike the NK cell activity against a wide range of tumors and normal cells, hybrid resistance is characterized by the immunogenetic specificity controlled by a set of unique noncodominant genes denoted as Hh. Two alternative hypotheses can account for the specificity. Thus, the specificity may reflect either the Hh restriction of effectors or the Hh gene control of mechanisms regulating non-Hh-restricted effector activity. In this study, therefore, we tested the recognition specificity of putative effectors mediating hybrid resistance in lethally irradiated H-2b/d and H-2b/k F1 hybrid mice to the engraftment of parental H-2b bone marrow. As a direct means of defining the effector specificity, rejection of parental bone marrow grafts was subjected to competitive inhibition in situ by irradiated tumor cells. Of the 16 independent lines of lymphoma and other hemopoietic tumor cells tested, the ability to inhibit hybrid resistance was the exclusive property of all tumors derived from mice homozygous for the H-2Db region, regardless of whether the tumor cells were susceptible or resistant to NK cell-mediated cytotoxicity in vitro. Four cell lines heterozygous for the H-2Db were noninhibitory, including one that is susceptible to natural killing. Pretreatment of the F1 hosts with an interferon inducer augmented the resistance with no alteration in the recognition specificity of effector cells. Therefore, natural resistance to parental H-2b bone marrow grafts was mediated by effectors restricted by the H-2Db/Hh-1b gene(s), and not by the nonrestricted NK cells detectable in conventional in vitro assays.
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This article has been cited by other articles:

• Kusunoki, Y., Kyoizumi, S., Honma, M., Kubo, Y., Ohnishi, H., Hayashi, T., Seyama, T. (2000). NK-Mediated Elimination of Mutant Lymphocytes that Have Lost Expression of MHC Class I Molecules. J. Immunol. 165: 3555-3563 [Abstract] [Full Text]  
• Johansson, M. H., Bieberich, C., Jay, G., Karre, K., Hoglund, P. (1997). Natural Killer Cell Tolerance in Mice with Mosaic Expression of Major Histocompatibility Complex Class I Transgene. JEM 186: 353-364 [Abstract] [Full Text]  
• Bordignon, C, Daley, J., Nakamura, I (1985). Hematopoietic histoincompatibility reactions by NK cells in vitro: model for genetic resistance to marrow grafts. Science 230: 1398-1401 [Abstract]  

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