T-cell receptor repertoire analysis in CVID patients post Comirnaty vaccination

Abstract

Common variable immunodeficiency (CVID) is one the most diagnosed primary immunodeficiencies (PID) with a complex etiology, characterized by low levels of serum immunoglobulins mainly due to B-cell deficiencies with potential T-cell dysregulations and abnormalities. This immune system dysfunction puts CVID patients at a higher risk for developing severe infections, including COVID-19. Despite its critical importance, their immune response to SARS-CoV-2 infection and vaccination remains unclear. Studying the T-cell-receptor (TCR) repertoire of these patients sheds light on the dynamics of their cellular immune response, knowing that T-cells recognize antigens through their TCR. In this study, we utilized high throughput sequencing to investigate and profile the TCR repertoire of PID patients, particularly those with CVID following the second dose of the Pfizer-BioNTech Comirnaty-BNT162b2 vaccine. We report on the diversity and clonality of TCR repertoires between diseased and healthy individuals post-vaccination. Investigating gene segment usage, we found a bias in the frequency of TCR V beta gene segment usage between patients and controls. Lastly, we examined the clonal expansion of T-cells following Spike-antigen (S Ag) stimulation to provide insights into the T-cell response post-vaccination.