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

Cole, David ORCID: https://orcid.org/0000-0003-0028-9396, Gallagher, Kathleen, Lemercier, Brigitte, Holland, Christopher J., Junaid, Sayed, Hindley, James Phillip, Wynn, Katherine Kay, Gostick, Emma, Sewell, Andrew K. ORCID: https://orcid.org/0000-0003-3194-3135, Gallimore, Awen Myfanwy ORCID: https://orcid.org/0000-0001-6675-7004, Ladell, Kristin Ingrid ORCID: https://orcid.org/0000-0002-9856-2938, Price, David ORCID: https://orcid.org/0000-0001-9416-2737, Gougeon, Marie-Lise and Godkin, Andrew James ORCID: https://orcid.org/0000-0002-1910-7567 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:	15 May 2024 01:12
URI:	https://orca.cardiff.ac.uk/id/eprint/37370

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