title: Secondary immunisation with high-dose heterologous peptide leads to CD8 T cell populations with reduced functional avidity.
abstract: Expansion of high- or low-avidity CD8 T cells in vitro inversely correlates with the concentration of peptide ligand present during culture. In contrast, the selective enrichment of high- or low-avidity T cell populations in vivo using peptide immunisation is not well documented. In our study, a single immunisation with different doses of wild-type peptide or a variant peptide able to stimulate CTL responses cross-reactive with wild-type peptide failed to shift the average avidity of the responding CD8 T cell population specific to either peptide. However, in contrast to homologous prime-boost immunisation, heterologous prime-boost immunisation incorporating high doses of the second immunogen resulted in peptide-specific CD8 T cell populations polarized toward a low average functional avidity. These data suggest that sequential exposure to structurally related viral peptides could impair rather than promote anti-viral immunity by lowering the avidity of the responding CD8 T cell population. This study has implications for improving vaccine strategies against viruses and tumours and enhances our understanding of heterologous immunity during sequential viral infection.
authors.affiliation: Centre for Immunology and Cancer Research, Princess Alexandra Hospital, University of Queensland, Woolloongabba, Brisbane, Australia.
authors.forename: Sharmal
authors.initials: S
authors.lastname: Narayan
authors.forename: Allison
authors.initials: A
authors.lastname: Choyce
authors.forename: Germain J P
authors.initials: GJ
authors.lastname: Fernando
authors.forename: Graham R
authors.initials: GR
authors.lastname: Leggatt
mesh_terms: D000818:Animals; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D005260:Female; D007117:Immunization, Secondary / Q000379:methods*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000276:immunology*; D010455:Peptides / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; D050725:Papillomavirus E7 Proteins; D010455:Peptides