Modification of the carboxy-terminal flanking region of a universal influenza epitope alters CD4⁺ T-cell repertoire selection.
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.
Institute of Infection and Immunity, Cardiff University School of Medicine, The Henry Wellcome Building, Cardiff CF14 4XN, Wales, UK.
David K
DK
Cole
Kathleen
K
Gallagher
Brigitte
B
Lemercier
Christopher J
CJ
Holland
Sayed
S
Junaid
James P
JP
Hindley
Katherine K
KK
Wynn
Emma
E
Gostick
Andrew K
AK
Sewell
Awen M
AM
Gallimore
Kristin
K
Ladell
David A
DA
Price
Marie-Lise
ML
Gougeon
Andrew
A
Godkin
D019921:Biotinylation; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D000939:Epitopes / Q000737:chemistry*; D005434:Flow Cytometry / Q000379:methods; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D007252:Influenza Vaccines / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology* / Q000821:virology; D008957:Models, Genetic; D008958:Models, Molecular; D008968:Molecular Conformation; D009975:Orthomyxoviridae / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry; D017434:Protein Structure, Tertiary; D020349:Surface Plasmon Resonance; D013696:Temperature; D013997:Time Factors
D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D007252:Influenza Vaccines; D010455:Peptides