Relevance of Peptide Avidity to the T Cell Receptor for Cytomegalovirus‐Specific Ex Vivo CD8 T Cell Cytotoxicity

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Abstract
CD8+ T cells contribute to the control of viral infection by several effector mechanisms, including lysis of virally infected cells and interferon (IFN)–γ secretion. Ex vivo cytotoxicity and potent secretion of IFN-γ in response to cytomegalovirus (CMV) epitope peptides was seen in freshly prepared unstimulated peripheral blood mononuclear cells from human immunodeficiency virus–infected patients with high T cell receptor (TCR)/peptide avidity. Lymphocytes with low TCR/peptide avidity had no ex vivo cytotoxicity, secreted minimal IFN-γ, and could not recognize autologous infected targets. Despite this, ex vivo responding and nonresponding patients had substantial frequencies of tetramer-positive and IFN-γ–secreting lymphocytes. Levels of activation and memory markers were also similar in tetramer-positive populations of both groups. However, cytolytic capacity remained in nonresponders; their lymphocytes regained cytotoxicity after in vitro stimulation with peptide without coactivators or interleukin-2. High-avidity CD8+ T cells are likely important in viral control, and their generation should be a goal of therapeutic vaccination

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