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Granzyme A, a granule-associated serine proteinase of activated cytotoxic T cells and natural killer cells, has been reported to play a critical role in DNA fragmentation of target cells. To address the question of the biological role of granzyme A, we have now generated a granzyme A-deficient mouse mutant by homologous recombination. Western blot analysis,(More)
A structural glycoprotein of lymphocytic choriomeningitis virus was obtained in pure form by immunoaffinity chromatography using a monoclonal antibody with high neutralizing activity. It blocked neutralization of viral infectivity by antibody and in polyacrylamide gel electrophoresis it migrated with an apparent molecular weight of 44 X 10(3). We conclude(More)
Lymphocytic choriomeningitis (LCM) virus-infected culture cells as targets were markedly reduced in numbers when incubated in vitro with spleen cells from LCM virus-immune mice, even if the cells were taken months after a subcutaneous immunizing infection of the donor animal. Spleen cells from mice persistently infected with LCM virus had no effect on(More)
After intravenous infection of mice, lymphocytic choriomeningitis virus multiplied in spleens and livers, attaining highest concentrations on days 4 to 6. The subsequent clearance was as rapid, and 8 to 10 days after inoculation, infectivity was usually below detectability. During the effector phase of virus elimination, both cytotoxic T-cell (CTL) activity(More)
Adult mice were infected by i.v. inoculation with 10(3) mouse infectious doses of lymphocytic choriomeningitis virus (LCM virus). Despite widespread replication of the agent, overt illness did not develop; histopathologic alterations were moderate. High virus concentrations were attained in the spleen, which was chosen for further study. Cytotoxic spleen T(More)
BALB/c and C57BL/6J mice were immunized with recombinant vaccines consisting of lymphocytic choriomeningitis virus CD8+ T-lymphocyte epitopes and a carrier protein. During challenge infection with WE strain lymphocytic choriomeningitis virus, mutants with alterations in distinct amino acid residues of the epitopic nonapeptides appeared and multiplied.(More)
The primary CTL response of BALB/c mice infected with the lymphocytic choriomeningitis (LCM) virus strain WE is directed exclusively against one major epitope, n118, whereas a viral variant, ESC, that does not express n118 induces CTL against minor epitopes. We identified one minor epitope, g283, that induces primary lytic activity in ESC-infected mice.(More)
Injection into mice of chimeric proteins consisting of a portion of either the simian virus 40 large tumor antigen or nonstructural protein 1 of influenza A virus or of the murine tumor suppressor p53 on one hand and T-cell epitopes of lymphocytic choriomeningitis virus on the other resulted in antiviral protective immunity, which was independent of the(More)
A solid phase immunoenzymatic technique was employed for detecting single IFN-gamma-producing cells (IFN-gamma PC) in the mouse. After infection with lymphocytic choriomeningitis virus or Listeria monocytogenes, the numbers of IFN-gamma PC in spleens began to rise on day 4, attained maxima on days 7 and 8, and declined thereafter. Negative selection in(More)