Preexisting memory CD4 T cells in naïve individuals confer robust immunity upon hepatitis B vaccination

eLife

Kris Laukens¹  Nicolas De Neuter¹  Pieter Meysman¹  Nina Keersmaekers²  Philippe Beutels²  Benson Ogunjimi³  Pierre Van Damme⁴  Geert Mortier⁵  Esther Bartholomeus⁵  Arvid Suls⁵  Hilde Jansens⁶  Aisha Souquette⁷  Paul G Thomas⁷  Marie-Paule Emonds⁸  Viggo Van Tendeloo⁹  George Elias^1,10  Evelien Smits^1,11  Hans De Reu^1,11  Eva Lion^1,11 

[1] Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing, University of Antwerp, Antwerp, Belgium;Adrem Data Lab, Department of Mathematics and Computer Science, University of Antwerp, Antwerp, Belgium;Biomedical Informatics Research Network Antwerp, University of Antwerp, Antwerp, Belgium;Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing, University of Antwerp, Antwerp, Belgium;Centre for Health Economics Research & Modeling Infectious Diseases, Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium;Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing, University of Antwerp, Antwerp, Belgium;Centre for Health Economics Research & Modeling Infectious Diseases, Vaccine & Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium;Antwerp Center for Translational Immunology and Virology (ACTIV), Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium;Department of Paediatrics, Antwerp University Hospital, Antwerp, Belgium;Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing, University of Antwerp, Antwerp, Belgium;Centre for the Evaluation of Vaccination (CEV), Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium;Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing, University of Antwerp, Antwerp, Belgium;Department of Medical Genetics, University of Antwerp, Antwerp, Belgium;Department of Clinical Microbiology, Antwerp University Hospital, Antwerp, Belgium;Department of Immunology, St. Jude Children's Research Hospital, Memphis, United States;Histocompatibility and Immunogenetic Laboratory, Rode Kruis-Vlaanderen, Mechelen, Belgium;Laboratory of Experimental Hematology (LEH), Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium;Laboratory of Experimental Hematology (LEH), Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium;Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing, University of Antwerp, Antwerp, Belgium;Laboratory of Experimental Hematology (LEH), Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium;Center for Cell Therapy and Regenerative Medicine, Antwerp University Hospital, Antwerp, Belgium;

关键词: CD4 T cell;    T cell receptor;    TCR repertoire;    vaccination;    Human;   

DOI  :  10.7554/eLife.68388

来源: eLife Sciences Publications, Ltd

【 摘 要 】

Antigen recognition through the T cell receptor (TCR) αβ heterodimer is one of the primary determinants of the adaptive immune response. Vaccines activate naïve T cells with high specificity to expand and differentiate into memory T cells. However, antigen-specific memory CD4 T cells exist in unexposed antigen-naïve hosts. In this study, we use high-throughput sequencing of memory CD4 TCRβ repertoire and machine learning to show that individuals with preexisting vaccine-reactive memory CD4 T cell clonotypes elicited earlier and higher antibody titers and mounted a more robust CD4 T cell response to hepatitis B vaccine. In addition, integration of TCRβ sequence patterns into a hepatitis B epitope-specific annotation model can predict which individuals will have an early and more vigorous vaccine-elicited immunity. Thus, the presence of preexisting memory T cell clonotypes has a significant impact on immunity and can be used to predict immune responses to vaccination.

【 授权许可】

CC BY