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  • Title: Relevance of peptide avidity to the T cell receptor for cytomegalovirus-specific ex vivo CD8 T cell cytotoxicity.
    Author: Villacres MC, Lacey SF, Auge C, Longmate J, Leedom JM, Diamond DJ.
    Journal: J Infect Dis; 2003 Sep 15; 188(6):908-18. PubMed ID: 12964124.
    Abstract:
    CD8(+) T cells contribute to the control of viral infection by several effector mechanisms, including lysis of virally infected cells and interferon (IFN)-gamma secretion. Ex vivo cytotoxicity and potent secretion of IFN-gamma 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-gamma, and could not recognize autologous infected targets. Despite this, ex vivo responding and nonresponding patients had substantial frequencies of tetramer-positive and IFN-gamma-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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