Enhanced detection of antigen-specific CD4+ T cells using altered peptide flanking residue peptide-MHC class II multimers

Holland, Christopher J., Dolton, Garry M., Scurr, Martin ORCID: https://orcid.org/0000-0002-4120-0688, Ladell, Kristin ORCID: https://orcid.org/0000-0002-9856-2938, Schauenburg, Andrea J., Miners, Kelly, Madura, Florian, Sewell, Andrew K. ORCID: https://orcid.org/0000-0003-3194-3135, Price, David A. ORCID: https://orcid.org/0000-0001-9416-2737, Cole, David K. ORCID: https://orcid.org/0000-0003-0028-9396 and Godkin, Andrew J. ORCID: https://orcid.org/0000-0002-1910-7567 2015. Enhanced detection of antigen-specific CD4+ T cells using altered peptide flanking residue peptide-MHC class II multimers. Journal of Immunology 195 (12) , pp. 5827-5836. 10.4049/jimmunol.1402787

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Abstract

Fluorochrome-conjugated peptide–MHC (pMHC) class I multimers are staple components of the immunologist’s toolbox, enabling reliable quantification and analysis of Ag-specific CD8+ T cells irrespective of functional outputs. In contrast, widespread use of the equivalent pMHC class II (pMHC-II) reagents has been hindered by intrinsically weaker TCR affinities for pMHC-II, a lack of cooperative binding between the TCR and CD4 coreceptor, and a low frequency of Ag-specific CD4+ T cell populations in the peripheral blood. In this study, we show that peptide flanking regions, extending beyond the central nonamer core of MHC-II–bound peptides, can enhance TCR–pMHC-II binding and T cell activation without loss of specificity. Consistent with these findings, pMHC-II multimers incorporating peptide flanking residue modifications proved superior for the ex vivo detection, characterization, and manipulation of Ag-specific CD4+ T cells, highlighting an unappreciated feature of TCR–pMHC-II interactions.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	Q Science > QR Microbiology > QR180 Immunology
Additional Information:	This is an open-access article distributed under the terms of the CC-BY 3.0 Unported license.
Publisher:	American Association of Immunologists
ISSN:	0022-1767
Funders:	Wellcome Trust
Date of First Compliant Deposit:	30 March 2016
Date of Acceptance:	8 October 2015
Last Modified:	15 May 2024 01:17
URI:	https://orca.cardiff.ac.uk/id/eprint/81950

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