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

David K. Cole, Kathleen Gallagher, Brigitte Lemercier, Christopher J. Holland, Sayed Junaid, James P. Hindley, Katherine K. Wynn, Emma Gostick, Andrew K. Sewell, Awen M. Gallimore, Kristin Ladell, David A. Price, Marie-Lise Gougeon and Andrew Godkin ()
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David K. Cole: Institute of Infection and Immunity, Cardiff University School of Medicine
Kathleen Gallagher: Institute of Infection and Immunity, Cardiff University School of Medicine
Brigitte Lemercier: Institut Pasteur, Antiviral Immunity, Biotherapy and Vaccine Unit
Christopher J. Holland: Institute of Infection and Immunity, Cardiff University School of Medicine
Sayed Junaid: Institute of Infection and Immunity, Cardiff University School of Medicine
James P. Hindley: Institute of Infection and Immunity, Cardiff University School of Medicine
Katherine K. Wynn: Institute of Infection and Immunity, Cardiff University School of Medicine
Emma Gostick: Institute of Infection and Immunity, Cardiff University School of Medicine
Andrew K. Sewell: Institute of Infection and Immunity, Cardiff University School of Medicine
Awen M. Gallimore: Institute of Infection and Immunity, Cardiff University School of Medicine
Kristin Ladell: Institute of Infection and Immunity, Cardiff University School of Medicine
David A. Price: Institute of Infection and Immunity, Cardiff University School of Medicine
Marie-Lise Gougeon: Institut Pasteur, Antiviral Immunity, Biotherapy and Vaccine Unit
Andrew Godkin: Institute of Infection and Immunity, Cardiff University School of Medicine

Nature Communications, 2012, vol. 3, issue 1, 1-8

Abstract: 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.

Date: 2012
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DOI: 10.1038/ncomms1665

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