Vaccination reshapes the virus-specific T cell repertoire in unexposed adults
Yi-Gen Pan1, Benjamas Aiamkitsumrit1, Laurent Bartolo1, Yifeng Wang1, Criswell Lavery2, Adam Marc2, Patrick V Holec3, C Garrett Rappazzo3, Theresa Eilola4, Phyllis A Gimotty5, Scott E Hensley4, Rustom Antia6, Veronika I Zarnitsyna7, Michael E Birnbaum3, Laura F Su8
- Department of Medicine, Division of Rheumatology, Perelman School of Medicine, Institute for Immunology, University of Pennsylvania, Philadelphia, PA 19104, USA.
- Department of Medicine, Division of Rheumatology, Perelman School of Medicine, Institute for Immunology, University of Pennsylvania, Philadelphia, PA 19104, USA; Corporal Michael J Crescenz VA Medical Center, Philadelphia, PA 19104, USA.
- Department of Biological Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
- Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
- Department of Biology, Emory University, Atlanta, GA, USA.
- Department of Microbiology and Immunology, Emory University, Atlanta, GA, USA.
- Department of Medicine, Division of Rheumatology, Perelman School of Medicine, Institute for Immunology, University of Pennsylvania, Philadelphia, PA 19104, USA; Corporal Michael J Crescenz VA Medical Center, Philadelphia, PA 19104, USA. Electronic address: laurasu@upenn.edu.
Abstract
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.
Presented By Yi-Gen Pan | ORCID iD