Preexisting memory CD4 T cells in naïve individuals confer robust immunity upon hepatitis B vaccination
George Elias, Pieter Meysman, Esther Bartholomeus, Nicolas De Neuter, Nina Keersmaekers, Arvid Suls, Hilde Jansens, Aisha Souquette, Hans De Reu, Marie‐Paule Emonds, Evelien Smits, Eva Lion, Paul G. Thomas, Geert Mortier, Pierre Van Damme, Philippe Beutels, Kris Laukens, Viggo Van Tendeloo, Benson Ogunjimi
Abstract
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.