Abstract
The diverse repertoire of T-cell receptors (TCR) plays a key role in the adaptive immune response to infections. Using TCR alpha and beta repertoire sequencing for T-cell subsets, as well as single-cell RNAseq and TCRseq, we track the concentrations and phenotypes of individual T-cell clones in response to primary and secondary yellow fever immunization - the model for acute infection in humans - showing their large diversity. We confirm the secondary response is an order of magnitude weaker, albeit ∼10 days faster than the primary one. Estimating the fraction of the T-cell response directed against the single immunodominant epitope, we identify the sequence features of TCRs that define the high precursor frequency of the two major TCR motifs specific for this particular epitope. We also show the consistency of clonal expansion dynamics between bulk alpha and beta repertoires, using a new methodology to reconstruct alpha-beta pairings from clonal trajectories.
Highlights
T-cells play a crucial role in the immune response to pathogens by mediating antibody formation and clearance of infected cells, and by defining an overall response strategy
The biological replicates of bulk peripheral blood mononuclear cells (PBMCs) were used to estimate the noise in the T-cell receptors (TCR) mRNA counts
Overall we found 1580 TCR beta and 1566 TCR alpha clonotypes significantly expanded after the primary immunization, respectively occupying 6.7% and 7.8% of the sampled TCR repertoire of bulk PBMCs in cumulative frequency at the peak of the response (Figure 1B,C)
Summary
T-cells play a crucial role in the immune response to pathogens by mediating antibody formation and clearance of infected cells, and by defining an overall response strategy. The specificity of T-cells is determined by the T-cell receptor (TCR), a heterodimer of alpha and beta protein chains. Genes for alpha and beta chains assemble in a random process of somatic V(D)J-recombination, which leads to a huge variety of possible TCRs (Murugan et al, 2012). The resulting diverse naıve repertoire contains T-cell clones that recognize epitopes of yet unseen pathogens, and can participate in the immune response to infection or vaccination. One of the best established models of acute viral infection in humans is yellow fever (YF) vaccination. The dynamics of primary T-cell response was investigated by various
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
