tetano
Editor, Senior Moderator
Nat Commun. 2012 Feb 7;3:665. doi: 10.1038/ncomms1665.
Modification of the carboxy-terminal flanking region of a universal influenza epitope alters CD4(+) T-cell repertoire selection.
Cole DK, Gallagher K, Lemercier B, Holland CJ, Junaid S, Hindley JP, Wynn KK, Gostick E, Sewell AK, Gallimore AM, Ladell K, Price DA, Gougeon ML, Godkin A.
Source
1] Institute of Infection and Immunity, Cardiff University School of Medicine, The Henry Wellcome Building, Cardiff CF14 4XN, Wales, UK. [2].
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 (HA(305-320)) 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.
PMID:
22314361
[PubMed - in process]
http://www.ncbi.nlm.nih.gov/pubmed/22314361
Modification of the carboxy-terminal flanking region of a universal influenza epitope alters CD4(+) T-cell repertoire selection.
Cole DK, Gallagher K, Lemercier B, Holland CJ, Junaid S, Hindley JP, Wynn KK, Gostick E, Sewell AK, Gallimore AM, Ladell K, Price DA, Gougeon ML, Godkin A.
Source
1] Institute of Infection and Immunity, Cardiff University School of Medicine, The Henry Wellcome Building, Cardiff CF14 4XN, Wales, UK. [2].
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 (HA(305-320)) 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.
PMID:
22314361
[PubMed - in process]
http://www.ncbi.nlm.nih.gov/pubmed/22314361