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Abstract

Lymphocytic choriomeningitis virus (LCMV) infection in mice provides a robust model for studying CD8⁺ T cell immunity. This dissertation demonstrates that vaccination with hydrogen peroxide–inactivated LCMV induces durable, protective CD8⁺ T cell responses with an altered immunodominance hierarchy compared to infection. Vaccine-induced CD8⁺ T cells exhibited enhanced multifunctional cytokine expression and conferred protection against chronic LCMV-Clone 13 challenge, mediated directly by CD8⁺ T cells. Peptide-based studies revealed unprecedented cross-reactivity among LCMV epitopes with minimal sequence homology. These findings establish whole-virus inactivation as a viable vaccine strategy for eliciting strong CD8⁺ T cell immunity and uncover novel cross-reactivity patterns in antiviral responses.

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