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Protein kinase inhibitors substantially improve the physical detection of T-cells with peptide-MHC tetramers

Lissina, Anna, Ladell, Kristin Ingrid, Skowera, Ania, Clement, Mathew, Edwards, Emily, Seggewiss, Ruth, van den Berg, Hugo A., Gostick, Emma, Gallagher, Kathleen, Jones, Emma, Melenhorst, J. Joseph, Godkin, Andrew James, Peakman, Mark, Price, David, Sewell, Andrew K. and Wooldridge, Linda 2009. Protein kinase inhibitors substantially improve the physical detection of T-cells with peptide-MHC tetramers. Journal of Immunological Methods 340 (1) , pp. 11-24. 10.1016/j.jim.2008.09.014

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Abstract

Flow cytometry with fluorochrome-conjugated peptide-major histocompatibility complex (pMHC) tetramers has transformed the study of antigen-specific T-cells by enabling their visualization, enumeration, phenotypic characterization and isolation from ex vivo samples. Here, we demonstrate that the reversible protein kinase inhibitor (PKI) dasatinib improves the staining intensity of human (CD8+ and CD4+) and murine T-cells without concomitant increases in background staining. Dasatinib enhances the capture of cognate pMHC tetramers from solution and produces higher intensity staining at lower pMHC concentrations. Furthermore, dasatinib reduces pMHC tetramer-induced cell death and substantially lowers the T-cell receptor (TCR)/pMHC interaction affinity threshold required for cell staining. Accordingly, dasatinib permits the identification of T-cells with very low affinity TCR/pMHC interactions, such as those that typically predominate in tumour-specific responses and autoimmune conditions that are not amenable to detection by current technology.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QR Microbiology > QR180 Immunology
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Uncontrolled Keywords: T cell, tetramer, low avidity CTL, cancer immunology, autoimmunity
Publisher: Elsevier
ISSN: 0022-1759
Date of First Compliant Deposit: 20 February 2018
Date of Acceptance: 11 September 2008
Last Modified: 07 Feb 2019 21:50
URI: http://orca.cf.ac.uk/id/eprint/26014

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