H-2 effects on cell-cell interactions in the response to single non-H-2 alloantigens. II. H-2D region control of H-7.1-specific stimulator function in mixed lymphocyte culture and susceptibility to lysis by H-7.1-specific cytotoxic cells

P. J. Wettstein, Jeffrey A Frelinger

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Abstract

The relative immunogenicity of the H-7.1 alloantigen has been shown in a previous communication to be regulated by a gene in the D region of the mouse major histocompatibility (H-2) complex. The level of relative immunogenicity was inferred from survival times of H-7.1-incompatible skin grafts donated by donors with different H-2 haplotype origins of H-2D region genes. In this communication we report the results of an extension of these previous investigations into the possible role of H-2D region genes in controlling the capacity of H-7.1 incompatible lymphocytes to stimulate H-7.1-specific mixed lymphocyte culture proliferation and generation of cytotoxic effector cells. The results reported herein demonstrate that the H-2D genotype of H-7.1-incompatible stimulator cells determines the relative H-7.1-specific capacity of those lymphocytes to stimulate H-7.1-specific proliferation of in vivo primed responder T cells in secondary mixed lymphocyte culture. H-2D(b)-bearing, H-7.1-incompatible stimulators were significantly more effective in stimulating H-7.1-specific proliferation than H-2D(d)-bearing stimulators. As expected, H-2D(b), H-7.1-incompatible stimulators were also more effective than H-2D(d) stimulators in generating H-7.1-specific cytotoxic effector cells. Further, the susceptibility of 51Cr-labeled, H-7.1-incompatible lymphoblast targets to H-7.1-specific lysis was similarly regulated by an H-2D gene. Reciprocal H-2 restriction (F1 cells are capable of killing only the cells bearing the immunizing cell parental H-2 haplotype) observed by other investigators for cytolysis of non-H-2-incompatible targets was not observed. H-2D(d)-bearing, H-7.1-incompatible stimulators stimulated generation of cytotoxic effectors capable of detectably lysing H-2D(b) but not H-2D(d)-bearing, H-7.1-incompatible targets. The impact of these observations on the proposed models for H-2 restriction of non-H-2 histocompatibility antigen-specific cytolysis is discussed.

Original languageEnglish (US)
Pages (from-to)1356-1366
Number of pages11
JournalJournal of Experimental Medicine
Volume146
Issue number5
Publication statusPublished - 1977
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology

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