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Naive CD8+ T cells give rise to cytotoxic T lymphocytes (CTLs), which promote the effective eradication of viruses and tumours. Although the past decades have seen enormous advances in cellular immunology, a precise understanding of the key elements that determine the specificity and magnitude of primary CTL responses has been lacking. However, recent technological advances have allowed us to more accurately identify, characterize and quantitate key determinants that define the specificity and magnitude of CD8+ T cell-mediated immunity. This Review discusses the technical and conceptual advances that have markedly changed our understanding of the determinants of primary CTL responses.
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