Through tetramer staining, Pan and Aiamkitsumrit et al. traced yellow fever virus (YFV)-specific CD4+ T cells in healthy, YFV-unexposed patients before and after YFV vaccination. YFV-specific T cells were detected prior to immunization and were heterogeneous in abundance, memory marker expression, and proliferation following vaccination. Although vaccination increased overall YFV-specific T cell frequency, TCR affinity, and clonotype diversity, the expansion of YFV-specific CD4+ T cell populations inversely correlated with their pre-vaccine frequencies; initially rare YFV-specific T cell populations selectively expanded, shifting the clonal repertoire.
Contributed by Alex Najibi
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.
Author Info: (1) Department of Medicine, Division of Rheumatology, Perelman School of Medicine, Institute for Immunology, University of Pennsylvania, Philadelphia, PA 19104, USA. (2) Department
Author Info: (1) Department of Medicine, Division of Rheumatology, Perelman School of Medicine, Institute for Immunology, University of Pennsylvania, Philadelphia, PA 19104, USA. (2) Department of Medicine, Division of Rheumatology, Perelman School of Medicine, Institute for Immunology, University of Pennsylvania, Philadelphia, PA 19104, USA. (3) Department of Medicine, Division of Rheumatology, Perelman School of Medicine, Institute for Immunology, University of Pennsylvania, Philadelphia, PA 19104, USA. (4) Department of Medicine, Division of Rheumatology, Perelman School of Medicine, Institute for Immunology, University of Pennsylvania, Philadelphia, PA 19104, USA. (5) 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. (6) 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. (7) Department of Biological Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA. (8) Department of Biological Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA. (9) Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. (10) Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. (11) Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. (12) Department of Biology, Emory University, Atlanta, GA, USA. (13) Department of Microbiology and Immunology, Emory University, Atlanta, GA, USA. (14) Department of Biological Engineering, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA. (15) 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.
