Exclusive involvement of H-2D(b) or H-2K(d) product in the interaction between T-killer lymphocytes and syngeneic H-2(b) or H-2(d) viral lymphomas

Abstract

It was demonstrated previously that the cytolysis of murine viral lymphoma cells by anti-murine sarcoma virus (MSV) syngeneic T-killer lymphocytes was restricted by some products of the H-2 complex. The respective role of the products of different regions of the H-2 complex were studied with six H-2(b) and three H-2(d) lymphomas induced by five different type C viruses. They were tested in a classical chromium release test against anti-MSV T-killer cells obtained from different inbred strains of mice, including several H-2 recombinants. Tumors o£ the H-2(b) haplotype were lysed only when effectors and target cells have in common the D(b) region. On the contrary an identity limited to the K end of the H-2 complex is necessary and sufficient in the H-2(d) haplotype. An in vitro restimulation of the spleen cells with concanavalin A strongly increased the activity of in vivo-primed T lymphocytes but did not provide any response for in vivo-primed but nonresponder cells. Preincubation of the tumor cells with anti-H-2 sera abolished the lysis by syngeneic anti-MSV effector lymphocytes. The same results were obtained by preincubating the H-2(b) targets with anti-H-2D(b), or the H-2(d) target with anti-H-2K(d). Preincubation with anti-H-2K(b) or anti- H-2D(d) were ineffective. These results show that the T-killer/target cells interaction in the MSV system involved some products of the H-2 complex which might be different with the various H-2 haplotypes and could possibly vary according to the antigenic specificity. A specific association of a viral product with a normal cellular structure, directed by the H-2 region during the viral budding could explain the observed results.

The role of gp70 in the target antigen recognized by murine leukemia virus immune cytotoxic T‐lymphocytes

“…This conclusion is consistent with the considerable evidence that has accumulated demonstrating that, in the systems studied so far, the MLVinduced tumor cell surface antigens responsible for eliciting the anti-tumor immune response in vivo are not carried on the MLV gp70 molecule (Alaba et al, 1979, and for review see Kurth et al, 1979). Further we (Zarling et al, 1978) and others (Gomard et al, 1978) have reported that a wide variety of high-titer xenogeneic antisera, raised against gp70 antigens purified from different MLV isolates, were unable to block the MLV-immune T, target-cell interaction. Most attempts to specifically block this interaction using purified MLV gp70 antigens have also only been partially successful Ting and Rogers, 1977); problems of non-specific inhibition by virion proteins in this type of assay have been reported (Shellam et al, 1976), and, as such, the results of Enjuanes et al (1979) must be interpreted with care.…”

“…Recently, however, Enjuanes et al (1979) achieved blocking of cytotoxicity with a purified Moloney MLV gp70 preparation, suggesting a role for gp70 in the target antigen. In contrast, we (Zarling et al, 1978) and others (Gomard et al, 1978) have shown that, in total, nine out of 10 tested high-titer xenogeneic antisera reactive with a wide range of type-specific gp70 antigens do not block FMR-MLV immune T, lysis of target cells; mouse antisera against the particular H-2 K and/or D-region encoded antigens expressed on the target cells almost completely abrogate cytotoxicity.…”

“…From extensive studies of the cytotoxic specificity of these FMR-MLV immune T, an insight into the complexity of the target antigen that is recognized has been obtained. Thus, for maximal target cell lysis to occur, the FMR-MLV-immune T, must recognize H-2 WD region encoded antigens and an antigen(s) usually only induced by the FMR group of MLV (Gomard et al, 1977(Gomard et al, , 1978; Herberman et al, 1974; Holden and Herberman, 1977).…”

Quantitative variations in the expression of H-2 antigens on murine leukemia virus-induced tumor cells can affect the H-2 restriction patterns of tumor-specific cytolytic T lymphocytes.

“…CTL specificity for target antigens was analyzed by two approaches: (a) addition of varying numbers of competitor target cells to the SXCr release cytotoxicity assay (5) and (b) addition of anti-H-2 sera at varying dilutions, in the absence of complement, to the 51Cr release cytotoxicity assay (1,11). The percentage of inhibition of CTL-mediated cytotoxicity by both approaches was calculated according to the formula: control -experiment/control × 100, where control was the specific cytotoxic activity detected in positive control wells; and experiment was the experimental cytotoxicity values obtained from wells containing competitor target cells or blocking antisera.…”

Detection of H‐2Dd and H‐2Kd molecules in purified rauscher leukemia virus

“…The latter argument is probably not valid, however, since in other experimental conditions, using low doses of infecting virus, anti-Friend CTL can be obtained as well in BALB/c mice (unpublished results). Furthermore, the association between H-2D molecules and virus particles is reportedly specific to the defective SFFV agent and not found with the competent helper virus (Chen and Lilly, 1979) while cross-reacting anti-FMR CTL can be produced with any type of FMR-inducing competent C-type viruses, all of them being restricted by H-2Db in the H-2b and H-2Kd in the H-2d haplotypes (Gomard et al, 1977). In the present experiments with Rauscher virions which induce typical FMRspecific H-2 restricted CTL (results not shown) an association was found mainly with H-2Dd which, in our experience, never functions as a CTL-restricting element, whereas the major restricting antigen H-2D was never detected.…”