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Modification of the carboxy-terminal flanking region of a universal influenza epitope alters CD4+ T-cell repertoire selection

Cole, David, Gallagher, Kathleen, Lemercier, Brigitte, Holland, Christopher J., Junaid, Sayed, Hindley, James Phillip, Wynn, Katherine Kay, Gostick, Emma, Sewell, Andrew K., Gallimore, Awen Myfanwy, Ladell, Kristin Ingrid, Price, David, Gougeon, Marie-Lise and Godkin, Andrew James 2012. Modification of the carboxy-terminal flanking region of a universal influenza epitope alters CD4+ T-cell repertoire selection. Nature Communications 3 , 665. 10.1038/ncomms1665

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Abstract

Human CD4+ αβ T cells are activated via T-cell receptor recognition of peptide epitopes presented by major histocompatibility complex (MHC) class II (MHC-II). The open ends of the MHC-II binding groove allow peptide epitopes to extend beyond a central nonamer core region at both the amino- and carboxy-terminus. We have previously found that these non-bound C-terminal residues can alter T cell activation in an MHC allele-transcending fashion, although the mechanism for this effect remained unclear. Here we show that modification of the C-terminal peptide-flanking region of an influenza hemagglutinin (HA305−320) epitope can alter T-cell receptor binding affinity, T-cell activation and repertoire selection of influenza-specific CD4+ T cells expanded from peripheral blood. These data provide the first demonstration that changes in the C-terminus of the peptide-flanking region can substantially alter T-cell receptor binding affinity, and indicate a mechanism through which peptide flanking residues could influence repertoire selection.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > QR Microbiology > QR180 Immunology
Q Science > QR Microbiology > QR355 Virology
Publisher: Nature Publishing Group
ISSN: 2041-1723
Last Modified: 10 Oct 2019 02:50
URI: http://orca.cf.ac.uk/id/eprint/37370

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