CEI: A Clonal Expansion Identifier for T-cell receptor clones following SARS-CoV-2 vaccination

TL;DR

This paper introduces CEI, a statistical method to identify and quantify T-cell receptor clones that expand in response to SARS-CoV-2 vaccination, providing insights into immune dynamics.

Contribution

We developed a novel statistical approach to detect vaccine-associated TCR clones and demonstrated its effectiveness with real data from vaccinated individuals.

Findings

Successfully identified vaccine-responsive TCR clones in peripheral blood.

Quantified clone-specific T-cell abundance changes post-vaccination.

Validated the method's robustness in vivo.

Abstract

Each T cell typically carries a specific T-cell receptor (TCR) that determines its specificity against an epitope presented by the HLA complex on a target cell. Antigenic challenge triggers the expansion of reactive cells within a diverse pool of T cells with randomly generated receptors, a process that results in epitope-driven shifts of TCR frequencies over time. Here, we analyze the effects of SARS-CoV-2 vaccination on the TCR populations in peripheral blood drawn from seven COVID-naive individuals, before vaccines were widely available. To identify SARS-CoV-2 vaccine-associated TCR sequences among the $\sim 10^{5}-10^{6}$ TCR sequences sampled before and after vaccination, we develop statistical criteria to detect significant increases in abundance of positive TCR clones. Application of our statistical methods shows a robust identification of TCR sequences that respond to SARS-CoV-2 vaccination in vivo, illustrating the feasibility of quantifying the clone-specific dynamics of T-cell abundance changes following immunological perturbations.