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

Maria C. Villacres, Simon F. Lacey, Catherine Auge, Jeff Longmate, John M. Leedom and Don J. Diamond
The Journal of Infectious Diseases
Vol. 188, No. 6 (Sep. 15, 2003), pp. 908-918
Published by: Oxford University Press
Stable URL: http://www.jstor.org/stable/30075636
Page Count: 11
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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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