Cell‐mediated cytotoxicity against ectromelia virus‐infected target cells. III. Role of the H‐2 gene complex

Abstract

The role of the H-2 gene complex in expression of cytotoxicity exerted by specific ectromelia-immune thymus-derived (T) cells against ectromelia-infected target cells was examined. A repertoire of inbred mouse strains (some congenic) including the H-2 haplotypes k, d, b, s, q, the recombinant H-2a(k/d) and F1 hybrids (k/b and d/b) were immunized with virus and their spleen cells tested 6 days later, at the peak of the primary response, against H-2k,H-2d and H-2b target cells. Significant specific cytotoxicity occurred only when the immune cell donors and the target cells shared all or part of the same H-2 gene complex. For example, H-2a (k/d) immune cells killed both H-2k and H-2d target cells. There was no detectable effect of the non-H-2 genetic background, H-2 public specificities, or the M-locus. Target cells infected with ectromelia virus exhibited quantitative or qualitative changes (or both) in expression of normal H-2 antigens as indicated by reduced susceptibility to killing by T cells activated against H-2 antigens in mixed lymphocyte culture. These data are consistent with the hypothesis that T cells in this system are responding to virus-induced, specific changes in antigens on infected cells which are controlled by genes in the H-2 complex; these genes seem likely to be those coding for H-2 private specificities, or genes closely linked to them.

Specificity studies on cytotoxic thymus-derived lymphocytes reactive with influenza virus-infected cells: evidence for dual recognition of H-2 and viral hemagglutinin antigens.

“…As shown in Fig. 2 (1)(2)(3)(4)(5). The extent to which the strain of influenza virus determines specificity is relevant to a consideration of the role played by H-2 antigens in T cell recognition of virus-infected target cells.…”

Bifunctional major histocompatibility-linked genetic regulation of cell-mediated lympholysis to trinitrophenyl-modified autologous lymphocytes.

“…Since the recent independent discoveries that viruses (8)(9)(10)(11)(12), and chemicals Tables I and II, however, semiallogeneic or allogeneic CML reactions with unmodified stimulating cells generated effectors which lysed to a variable extent (8 .1-23 .1%) any TNP-modified target spleen cell . This observation illustrates the importance of using only syngeneic mixtures of responder and stimulating cells in the sensitization phase of the CML .…”

Effects of Thymus‐independent (B) Cells and the H‐2 Gene Complex on Antiviral Function of Immune Thymus‐derived (T) Cells

“…Ectromelia virus stocks of both attenuated (Hampstead egg) and virulent (Moscow) strains, techniques of cell transfer, virus titration in tissues and in vitro cytotoxicity assays have been described in detail elsewhere (Blanden, 1970(Blanden, , 1971a(Blanden, , 1971bGardner, Bowern andBlanden, 1974a, 1975). Significance levels were determined by Student's "t" tests.…”

“…Experiments described in detail elsewhere have shown that specific T cellmediated cytotoxicity against ectromelia-infected target cells in vitro is efficiently expressed only when the T cell donors and target cells share at least a part of the same H-2 gene complex (Blanden, 1974b;Gardner et al, 1974bGardner et al, , 1975. To determine whether the same basic rules apply in vivo, cell transfer experiments were performed; 6-day immune spleen cells were injected i.v.…”