Immunogenetics

Ährlund-Richter, Lars; Klein, George; Klein, Eva

doi: 10.1007/bf00952961pmid: 6618531

YAC is a Moloney-virus-induced lymphoma of strain A/Sn origin that is highly sensitive to natural killing (NK) in vitro and NK-mediated hybrid resistance in vivo. Previous studies have shown that hybrid resistance is under polygenic control that includes bothH-2-linked and non-H-2-linked factors. For further analysis on the genetics and immunology of hybrid resistance, we are at present developing congenic resistant lines on an A/Sn strain background. Following an outcross to a strain that conveys strong hybrid resistance on the F1 offspring, the mice are challenged with small viable inocula of YAC. Survivors are backcrossed to A/Sn. This is followed by repeated YAC challenge and backcrossing. We now report the successful establishment of a first resistant strain, designated A.LRA. It is relatively resistant to small inocula of YAC cells due to a single, non-H-2-linked dominant gene introduced from the C57L strain.

O'Neill, Helen C.; Blandenr, R. V.; O'Neill, T. J.

doi: 10.1007/bf00952964pmid: 6311733

Several B 10 strains of mice, recombinant at theH-2 locus, have been shown to differ in their resistance to infection with ectromelia virus, a natural mouse pathogen. Of 10 strains, 1310, B 10.A(2R), B10.A(4R) and B10.D2 were the most resistant, while B10.G and B 10.A(5R) were the most susceptible. Other strains were intermediate between these extremes. Several genes conferring resistance have been mapped toDb in B10.A(2R),KkI-AkI-Bk in B10.A,I-Jb in B10.A(2R) and toDd in B 10.T(6R). In general, death among susceptible strains was not a consequence of acute liver necrosis as in other non-B10 strains, and occurred randomly from 8–14 days after infection. The exact cause of death is unknown but is characterized by persisting high titers of virus in the spleen and sometimes the liver, despite an ongoing immune response indicated by strong cytotoxic T-cell activity detectable in the spleens of all mice. The most resistant B10 and B10.A(2R) strains cleared virus from the spleen and liver by 8 days after infection. Analysis of infection in chimeric mice indicates thatH-2 genes, which determine susceptibility to virus persistence in the spleen, operate via radiosensitive cells of the lymphomyeloid system. This evidence, together with several examples ofH-2-linked differences in cytotoxic T-cell responsiveness between resistant and susceptible strains, is consistent with the hypothesis that the mechanism by whichH-2 genes control resistance to ectromelia virus in B10 strain mice is by their influence on the effectiveness of a cell-mediated immune response.