Search

Examines aspects of negative selection with mice expressing a transgenic T-cell receptor with specificity for lymphocytic choriomeningitis virus (LCMV) glycoprotein in association with the class 1 H-2Db molecule. Variant LCMVs were also tested for their ability to elicit antiviral responses in transgenic mice in vivo and in vitro.

Demonstrates that viruses can, in principle, escape the immunosurveillance of virus-specific cytotoxic T cells by mutations that alter the relevant T-cell epitope. Mice transgenic for a virus-specific TCR; Virus elimination; Virus variants; Pointmutations within the T-cell epitope; Discussion.

Discusses evidence that shows the predominant double-positive (CD4+CD8+) stage in transgenic mice can be subdivided into low and intermediate stages. Positively selected T-cells; Evidence of occurrence of negative selection.

Studies T-cell tolerance in transgenic mice expressing a T-cell receptor with double specificities for lymphocytic choriomeningitis virus (LCMV)-H-2Db and for the mixed-lymphocyte stimulatory (Mlsa) antigen. Research methods; Results; Discussion.

Viruses that are non- or poorly cytopathic have developed various strategies to avoid elimination by the immune system and to persist in the host. Acute infection of adult mice with the noncytopathic lymphocytic choriomeningitis virus (LCMV) normally induces a protective cytotoxic T-cell response that also causes immunopathology. But some LCMV strains (such as DOCILE (LCMV-D) or Cl-13 Armstrong (Cl-13)) derived from virus carrier mice tend to persist after acute infection of adult mice without causing lethal immunopathological disease. Tendency to persist correlates with tropism, rapidity of virus spread and virus mutations. We report here that these LCMV isolates may persist because they induce most of the specific antiviral CD8+ cytotoxic T cells so completely that they all disappear within a few days and therefore neither eliminate the virus nor cause lethal immunopathology. The results illustrate that partially and sequentially induced (protective) immunity or complete exhaustion of T-cell immunity (high zone tolerance) are quantitatively different points on the scale of immunity; some viruses exploit the latter possibility to persist in an immunocompetent host.