Vaccination reshapes the virus-specific T cell repertoire in unexposed adults
Immunity, 2021•cell.com
We examined how baseline CD4+ T cell repertoire and precursor states impact responses to
pathogen infection in humans using primary immunization with yellow fever virus (YFV)
vaccine. YFV-specific T cells in unexposed individuals were identified by peptide-MHC
tetramer staining and tracked pre-and post-vaccination by tetramers and TCR sequencing. A
substantial number of YFV-reactive T cells expressed memory phenotype markers and
contained expanded clones in the absence of exposure to YFV. After vaccination, pre …
pathogen infection in humans using primary immunization with yellow fever virus (YFV)
vaccine. YFV-specific T cells in unexposed individuals were identified by peptide-MHC
tetramer staining and tracked pre-and post-vaccination by tetramers and TCR sequencing. A
substantial number of YFV-reactive T cells expressed memory phenotype markers and
contained expanded clones in the absence of exposure to YFV. After vaccination, pre …
Summary
We examined how baseline CD4+ T cell repertoire and precursor states impact responses to pathogen infection in humans using primary immunization with yellow fever virus (YFV) vaccine. YFV-specific T cells in unexposed individuals were identified by peptide-MHC tetramer staining and tracked pre- and post-vaccination by tetramers and TCR sequencing. A substantial number of YFV-reactive T cells expressed memory phenotype markers and contained expanded clones in the absence of exposure to YFV. After vaccination, pre-existing YFV-specific T cell populations with low clonal diversity underwent limited expansion, but rare populations with a reservoir of unexpanded TCRs generated robust responses. These altered dynamics reorganized the immunodominance hierarchy and resulted in an overall increase in higher avidity T cells. Thus, instead of further increasing the representation of dominant clones, YFV vaccination recruits rare and more responsive T cells. Our findings illustrate the impact of vaccines in prioritizing T cell responses and reveal repertoire reorganization as a key component of effective vaccination.
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