The T cell receptor repertoire reflects the dynamics of the immune response to vaccination
This article has been Reviewed by the following groups
Discuss this preprint
Start a discussion What are Sciety discussions?Listed in
- Evaluated articles (ScreenIT)
Abstract
Early, high-resolution metrics are needed to ascertain the immune response to vaccinations. The T cell receptor (TCR), a heterodimer of one α and one β chain, is a promising target, with the complete TCR repertoire reflecting the T cells present in an individual. To this end, we developed Tseek, an unbiased and accurate method for profiling the TCR repertoire by sequencing the TCR α and β chains and developing a suite of tools for repertoire analysis. An added advantage is the ability to non-invasively analyze T cells in peripheral blood mononuclear cells (PBMCs). Tseek and the analytical suite were used to explore the T cell response to both the COVID-19 mRNA vaccine (n=9) and the seasonal inactivated Influenza vaccine (n=5) at several time points. Neutralizing antibody titers were also measured in the covid vaccine samples. The COVID-19 vaccine elicited a broad T cell response involving multiple expanded clones, whereas the Influenza vaccine elicited a narrower response involving fewer clones. Many distinct T cell clones responded at each time point, over a month, providing temporal details lacking in the antibody measurements, especially before the antibodies are detectable. In individuals recovered from a SARS-CoV-2 infection, the first vaccine dose elicited a robust T cell response, while the second dose elicited a comparatively weaker response, indicating a saturation of the response. The physical symptoms experienced by the recipients immediately following the vaccinations were not indicative of the TCR/antibody responses. The TCR responses broadly presaged the antibody responses. We also found that the TCR repertoire acts as an individual fingerprint: donors of blood samples taken years apart could be identified solely based upon their TCR repertoire, hinting at other surprising uses the TCR repertoire may have. These results demonstrate the promise of TCR repertoire sequencing as an early and sensitive measure of the adaptive immune response to vaccination, which can help improve immunogen selection and optimize vaccine dosage and spacing between doses.
Article activity feed
-
SciScore for 10.1101/2021.12.09.471735: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Antibodies Sentences Resources Vaccine-elicited anti-SARS-CoV-2 antibody responses were quantified using the GenScript SARS-CoV-2 Neutralization sVNT cPASS TM Kit (GenScript Catalog #L00847-5), which effectively measures the ability of patient plasma to block the interaction between the receptor binding domain (RBD) of the SARS-CoV-2 spike protein and its receptor angiotensin converting enzyme-2 (ACE2), according to manufacturer’s instructions. anti-SARS-CoV-2suggested: NoneSARS-CoV-2 spike protein and its receptor angiotensin converting enzyme-2 (ACE2)suggested: NoneEach dilution was incubated with recombinant horse radish … SciScore for 10.1101/2021.12.09.471735: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
NIH rigor criteria are not applicable to paper type.Table 2: Resources
Antibodies Sentences Resources Vaccine-elicited anti-SARS-CoV-2 antibody responses were quantified using the GenScript SARS-CoV-2 Neutralization sVNT cPASS TM Kit (GenScript Catalog #L00847-5), which effectively measures the ability of patient plasma to block the interaction between the receptor binding domain (RBD) of the SARS-CoV-2 spike protein and its receptor angiotensin converting enzyme-2 (ACE2), according to manufacturer’s instructions. anti-SARS-CoV-2suggested: NoneSARS-CoV-2 spike protein and its receptor angiotensin converting enzyme-2 (ACE2)suggested: NoneEach dilution was incubated with recombinant horse radish peroxidase (HRP)-conjugated RCB for 30 minutes at 37°C to allow antibody/RCB binding, transferred to human ACE2 coated assay microtiter plates, and incubated for 15 minutes at 37°C for 15 minutes. antibody/RCBsuggested: NoneSample absorbances were compared to the neutralization curve of a commercially available anti-SARS-CoV-2 RCB monoclonal antibody (GenScript, Catalog # A02051) of known concentration to extrapolate antibody titers, according to manufacturer’s protocol. anti-SARS-CoV-2 RCBsuggested: NoneSoftware and Algorithms Sentences Resources The quality and quantity were checked using the RNA Bioanalyzer Nano (Agilent Biotechnologies). Agilent Biotechnologiessuggested: NoneResults from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Caveats: The fundamental assumption in our analysis is that the abundance of vaccine reactive TCR α and β clones corresponds to binding efficiency to their cognate viral epitope. Implicit in this assumption is that there is an approximately one-to-one mapping between TCR CDR3 and epitopes. Clustering CDR3 by homology (Methods) did not affect our trees, nor did it significantly change the number of reactive clones but clustering in this manner might also not be sufficient in any case, since it might not identify all clones with common epitope targets, as there are cases where non-homologous clones that share targets, and homologous clones that have completely different targets.
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- No funding statement was detected.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
-
