Summary
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 vaccine specific model can predict which individuals will have an early and more vigorous vaccine-elicited immunity. Thus, the presence of preexisting memory T clonotypes has a significant impact on immunity and can be used to predict immune responses to vaccination.
Competing Interest Statement
Parts of the contents of this manuscript form the topic of patent EPO 19159931.5. VVT is an employee of Johnson & Johnson since 1/11/2019 and remains currently employed at the University of Antwerp.
Footnotes
Footnotes: This work was funded by
University of Antwerp [BOF Concerted Research Action (PS ID 30730) Methusalem funding; Industrial Research Fund SBO].
Research Foundation Flanders (1861219N grant to B. Ogunjimi and FWO SB grant to N. De Neuter).
ALSAC at St. Jude Children’s Research Hospital and by HSN272201400006C and R01AI107625 from the National Institute of Allergy and Infectious Disease.