International Immunology, Vol 10, 211-222, Copyright © 1998 by Oxford University Press
C Gelder, M Davenport, M Barnardo, T Bourne, J Lamb, B Askonas, A Hill and K Welsh
Influenza A/Beijing/32/92 (H3N2) haemagglutinin (HA)-specific short- term
CD4+ T cell lines were generated from six unrelated HLA-DR0701, 1501
positive adults (aged 27-60 years) 3 months following administration of an
influenza subunit vaccine containing HA A/Beijing/32/92. Epitope
recognition was examined using 118 HA A/Beijing/32/92-specific 16mer
peptides which overlapped by 11 residues and which spanned the entire
molecule. Following influenza vaccination the donors recognized identical
HA peptides. The selected peptides represented HA regions which have been
free from extensive drift mutation since the emergence of human H3N2
influenza A strains. Using DAP DR7.0701 cells (a murine cell line
expressing HLA-DR0701) as antigen-presenting cells the majority of CD4+ T
cell responses were shown to be HLA-DR0701 restricted. The relationship
between HA peptide recognition and relative strength of HA
peptide-HLA-DR0701 binding was then explored in a competition assay with
biotinylated CLIP peptide. Although peptides representing dominant HA
epitopes bound to DR0701, the relationship between relative strength of
binding and immunodominance was complex, and many strongly binding
peptides, particularly those with glycosylation sites and showing
inter-strain variation, were not recognized. These results illustrate the
control HLA class II exerts over CD4+ T cell HA epitope selection in
unrelated adult humans. Immunodominance appears not to be directly related
to the relative strength of HA peptide-HLA class II binding, and thus
reflects complex interactions between antigen processing, intracellular
competition for HLA binding, TCR repertoires and repeated exposure to
different strains of influenza A viruses.
ARTICLES
Six unrelated HLA-DR-matched adults recognize identical CD4+ T cell epitopes from influenza A haemagglutinin that are not simply peptides with high HLA-DR binding affinities
Department of Medicine, University of Wales College of Medicine, Cardiff, UK.
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