title: Diversification of the antigen-specific T cell receptor repertoire after varicella zoster vaccination.
abstract: Diversity and size of the antigen-specific T cell receptor (TCR) repertoire are two critical determinants for successful control of chronic infection. Varicella zoster virus (VZV) that establishes latency during childhood can escape control mechanisms, in particular with increasing age. We examined the TCR diversity of VZV-reactive CD4 T cells in individuals older than 50 years by studying three identical twin pairs and three unrelated individuals before and after vaccination with live attenuated VZV. Although all individuals had a small number of dominant T cell clones, the breadth of the VZV-specific repertoire differed markedly. A genetic influence was seen for the sharing of individual TCR sequences from antigen-reactive cells but not for repertoire richness or the selection of dominant clones. VZV vaccination favored the expansion of infrequent VZV antigen-reactive TCRs, including those from naïve T cells with lesser boosting of dominant T cell clones. Thus, vaccination does not reinforce the in vivo selection that occurred during chronic infection but leads to a diversification of the VZV-reactive T cell repertoire. However, a single-booster immunization seems insufficient to establish new clonal dominance. Our results suggest that repertoire analysis of antigen-specific TCRs can be an important readout to assess whether a vaccination was able to generate memory cells in clonal sizes that are necessary for immune protection.
authors.affiliation: Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, CA 94305, USA. Department of Medicine, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Qi
authors.affiliation: Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, CA 94305, USA. Department of Medicine, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA.
authors.forename: Mary M
authors.initials: MM
authors.lastname: Cavanagh
authors.affiliation: Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, CA 94305, USA. Department of Medicine, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA.
authors.forename: Sabine
authors.initials: S
authors.lastname: Le Saux
authors.affiliation: Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, CA 94305, USA. Department of Medicine, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: NamKoong
authors.affiliation: Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, CA 94305, USA. Department of Medicine, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA.
authors.forename: Chulwoo
authors.initials: C
authors.lastname: Kim
authors.affiliation: Department of Medicine, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA.
authors.forename: Emerson
authors.initials: E
authors.lastname: Turgano
authors.affiliation: Department of Statistics, Stanford University, Stanford, CA 94305, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pathology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Division of Infectious Diseases, Department of Pediatrics, Stanford University, Stanford, CA 94305, USA.
authors.forename: Sally
authors.initials: S
authors.lastname: Mackey
authors.affiliation: Department of Medicine, Stanford Prevention Research Center, Stanford University, Stanford, CA 94305, USA.
authors.forename: Gary E
authors.initials: GE
authors.lastname: Swan
authors.affiliation: Division of Infectious Diseases, Department of Pediatrics, Stanford University, Stanford, CA 94305, USA.
authors.forename: Cornelia L
authors.initials: CL
authors.lastname: Dekker
authors.affiliation: Department of Statistics, Stanford University, Stanford, CA 94305, USA. Department of Biomedical Data Science, Stanford University, Stanford, CA 94305, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Olshen
authors.affiliation: Department of Pathology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Boyd
authors.affiliation: Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, CA 94305, USA. Department of Medicine, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA.
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: Weyand
authors.affiliation: Department of Biomedical Data Science, Stanford University, Stanford, CA 94305, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Tian
authors.affiliation: Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, CA 94305, USA. Department of Medicine, VA Palo Alto Health Care System, Palo Alto, CA 94304, USA. jgoronzy@stanford.edu.
authors.forename: Jörg J
authors.initials: JJ
authors.lastname: Goronzy
mesh_terms: D000956:Antigens, Viral / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D019433:Chickenpox Vaccine / Q000276:immunology*; D002999:Clone Cells; D014645:Herpesvirus 3, Human / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D014611:Vaccination
chemical_list: D000956:Antigens, Viral; D019433:Chickenpox Vaccine; D011948:Receptors, Antigen, T-Cell