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|Title:||Genetic and Viral Specificity of the Cell-Mediated Immune Response to Pichinde Virus in Mice|
|Advisor:||Rosenthal, K. L.|
|Abstract:||This study was undertaken to examine the genetic and viral target specificity of the cell-mediated immune response to Pichinde virus (PV) in mice, to ultimately facilitate the cloning of anti-PV cytotoxic T lymphocytes (CTL). Cloned populations provide a system for the study of the generation, function, and mechanism of action of CTL in viral infections. CTL are often genetically restricted to either the K or D end of H-2 Class I. Cytotoxicity assays performed using primary immunized murine splenocytes showed predominant restriction to the K locus in H-2ᵇ C57B1/6 mice. In limiting dilution assays, a significant population of anti-PV CTL (approximately one-half) were regulated by H-2Kᵇ. A panel of temperature sensitive (ts) mutants of wild type (wt) PV was used to study the viral target specificity of anti-PV CTL. These mutants were grouped according to surface expression and internal production of viral molecules as detected by indirect immunofluorescence and polyacrylamide gel electrophoresis respectively. Cytotoxicity assays with target cells infected with these mutants provided equivocal results regarding whether the major target antigen was an internally or externally expressed viral protein. The results suggest that surface expression of viral proteins may be related to target specificity in the anti-PV cytotoxic response. One temperature sensitive mutant, ts 488, provided a superior target for H-2ᵇ effectors than wt PV when used to infect 5R (H-2Kᵇ compatible) target cells. Limiting dilution studies indicated that anti-ts 488 CTL were predominantly regulated by H-2Kᵇ: approximately three-quarters of the CTL precursors were restricted to that end. Furthermore, limiting dilution assays indicated that ts 488 and wt PV were not fully cross reactive in generating lytic effectors. As a result, the mutant might not facilitate the generation of cloned lines of anti-wt PV CTL. The mutant and its augmented regulation by H-2Kᵇ may provide a novel system for the examination of the association and recognition of viral plus "self" antigens at the level of antigen presentation and target identification.|
|Appears in Collections:||Digitized Open Access Dissertations and Theses|
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