Biology subjects

Kuznetsova, M.

Publications and source records attributed to Kuznetsova, M..

7 recordsLinked to original sources

bioRxiv2026

Longitudinal Profiling of CD4⁺ T Cell Responses Following de novo Yellow Fever Vaccination

The yellow fever 17D vaccine is one of the most successful live-attenuated viral vaccines, yet the cellular mechanisms underlying its long-term protection remain not fully understood. This study provides a longitudinal analysis of the human CD4+ T cell and IgG response following de novo yellow fever vaccination by focusing. Peripheral blood mononuclear cells (PBMCs) from 49 vaccinated individuals were stimulated with yellow fever (YF) and control peptide pools across four timepoints: pre-vaccination/baseline (D1), day 22 (D22), day 43 (D43), and one year (D365) post-vaccination. Activation-induced marker (AIM) assays confirmed robust activation of CD4+ T cells following yellow fever peptide stimulation, peaking at day 22 post-vaccination and subsequently declining. T-cell receptor (TCR{beta}) sequencing of AIM-sorted CD4+ T cells showed a transient increase in clonal diversity at D22, consistent with broad epitope targeting and early polyclonal expansion. This was followed by repertoire contraction, which could indicate the persistence of a limited set of dominant clonotypes responsible for immune memory formation. TCR repertoires remained largely private over time, indicating a mostly individualized immune response. Next, serological analyses revealed a robust and highly yellow fever virus (YFV)-specific IgG response. Antibody levels peaked within the D22-D43 window and remained elevated at one year post-vaccination. Cross-reactivity toward other flaviviruses was limited, suggesting an antigen-specific humoral response. Together, these findings characterize the longitudinal dynamics of the CD4+ T cell and IgG response following de novo yellow fever vaccination and provide insights into the mechanisms contributing to durable antiviral immunity.

immunology↗

bioRxiv2026

The T cell receptor repertoire captures healthy aging and CMV independently from epigenetic clocks

Human aging is the process through which numerous biological changes occur during life, affecting various processes. In some elderly individuals, this functional decline becomes more pronounced, leading to frailty, a condition characterised by reduced physiological reserves and increased vulnerability to stress. With the global rise of life expectancy, identification of biomarkers for healthspan and frailty are becoming more important. In this study, we directly compare two molecular readouts, namely the T cell receptor (TCR) repertoire and epigenetic clocks, on their ability to discern healthy aging. On blood samples from sixteen individuals, across age-matched healthy elderly and frail individuals, both TCR sequencing and epigenetic profiling were performed. A significantly higher TCR repertoire diversity in the CD4+ T cells differentiated the healthy elderly individuals from the frailty ones. Epigenetic clock signatures of biological relative to chronological ageing rate, did not show a clear difference between both groups. However, when taking into account the CMV-serostatus, a significant increase in epigenetic aging could be observed in the CMV-seropositive individuals. Our results support a clear hypothesis on the role of CMV infection in the healthy aging of the immune system. In healthy elderly, CMV is typically controlled by CD4+ T cells, however, in the frail elderly, the burden of managing the infection shifts to the CD8+ T cells. This change is marked by two key changes: a decrease in TCR diversity for seropositive individuals compared to seronegative individuals, as well as an increase in the fraction of CMV-associated TCRs within the CD8+ T cells. These findings contribute to our understanding of aging and provide insight into how CMV-infection may affect healthy aging and frailty. They also underline the crucial role of the immune system in healthy aging and the value of further investigating ageing-related health/disease patterns in the TCR repertoire to determine healthspan/lifespan.

immunology↗

bioRxiv2025

T cell-microbiome associations captured through T cell receptor convergence analysis

The gut microbiome modulates mucosal immunity, yet how specific bacterial taxa shape the diversity and specificity of T cell receptor (TCR) repertoires remains poorly understood. Existing approaches emphasize single-species effects or broad immune features, without pinpointing which microbes drive specific T cell clonotypes. We present AIRRWAS, a computational framework that integrates TCR-microbiome interaction analysis with targeted in vitro validation to detect genus-level TCR convergence. Applied to three independent cohorts, AIRRWAS identified reproducible associations between convergent TCR clusters and 21 bacterial genera spanning core commensals, probiotics and taxa with immunomodulatory roles. Predicted clonotypes were enriched within the TCR-microbiome interaction network and preferentially activated by genus-matched stimuli, eliciting different functional T cell responses. These findings demonstrate that distinct repertoires can share genus-specific TCR motifs, enabling detection of shared immune signatures. AIRRWAS can map these TCR- microbiome interactions, laying the groundwork for biomarker discovery immune monitoring and the development of microbiome-targeted therapies.

bioinformatics↗

bioRxiv2025

Generation of a T cell receptor, cytokine and cell repertoire synovial fluid atlas to define commonalities and dissimilarities between arthritic diseases through systems immunology approaches

Although different chronic arthritic diseases are defined by clinical factors like gender, psoriasis and auto-antibodies, the biology of inflamed joints while comparing the different diseases remains neglected. Here, after curating an inflamed joint derived T-cell receptor (TCR) database, our new TRIASSIC tool identified 66303 significantly convergent TCR clonotypes. Clustering TCR clonotypes showed that synovial fluid convergence clusters (SFCCs) characterized HLA-B27+ mediated diseases (spondyloarthritis, SpA, and enthesitis-related juvenile idiopathic arthritis, JIA-ERA), Lyme arthritis and oligoarticular JIA. Single-cell transcriptomics and bulk proteomics showed upregulated interferon type I and II and TNF- pathways in oJIA. Adult and juvenile psoriatic arthritis, (JIA-)PsA, was characterized by upregulated HSP expression in monocytes and TXNIP in T-cells. We discovered an abundance of CCL5 expressing CD8+ T-cells in SF from HLA-B27+ JIA-ERA and SpA patients. JIA-ERA patients showed upregulation of CD74 and LGALS1 in Th1 and Th17 cells and IGHV7-4.1 in B-cells. oJIA patients shared a TRBV28 RG-motif on CXCL13 producing helper T-cells. Rheumatoid arthritis and (JIA-)PsA patients carried EBV-reactive cytotoxic CD8+ T-cells. Annexin signalling was shown to be important in the intercellular communication for all arthritis groups. Collectively, our work showed that chronic arthritis is characterized by both disease-specific and broadly shared mechanisms.

immunology↗

bioRxiv2024

Bridging immunotypes and enterotypes using a systems immunology approach

Unveiling the systemic effects of disease and health requires an holistic approach that has mainly revolved around well established, directly determinable molecular relationships such as the protein synthesis cascade and epigenetic mechanisms. In this study, involving 394 individuals, we found direct linkage of branches spanning human biological functions often not studied in conjunction, using clinical data, gut microbial abundances, blood immune cell repertoires, blood transcriptomic and blood T cell receptor data. Contrary to current paradigms, we demonstrate that immunotypes and enterotypes are orthogonal, likely fulfilling distinct roles in maintaining homeostasis, only bridged via the blood transcriptome. We also identified two distinct inflammatory profiles: the first driven by interferon signalling and the other characterised by non-viral, NF-kB and IL-6 markers. Lastly, we present compelling data showing strong associations of the Ruminococcaceae and Christensenellaceae bacteria with a healthy immunotype and transcriptomic pattern, highlighting their potential role in immune health. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=194 HEIGHT=200 SRC="FIGDIR/small/625344v1_ufig1.gif" ALT="Figure 1"> View larger version (52K): org.highwire.dtl.DTLVardef@c6b5eorg.highwire.dtl.DTLVardef@15d0c3forg.highwire.dtl.DTLVardef@1cf29eeorg.highwire.dtl.DTLVardef@1c9ff8d_HPS_FORMAT_FIGEXP M_FIG C_FIG

systems biology↗

bioRxiv2024

Linking myelin and Epstein-Barr virus specific immune responses in multiple sclerosis: insights from integrated public T cell receptor repertoires

The autoimmune responses in multiple sclerosis (MS), particularly those mediated by T cells targeting CNS-derived antigens, are broadly recognized. However, the defining triggers underlying these responses remain poorly understood. Epstein-Barr virus (EBV) infection has emerged as a primary risk factor for MS, suggesting a potential role for molecular mimicry in which EBV-specific immune responses cross-react with myelin antigens. In this study, we analyzed the T cell receptor (TCR) repertoires of MS patients (n = 129) and controls (n = 94) from public datasets, to explore the relationship between EBV-specific and myelin-specific T cell responses. Our analysis identified clusters of TCRs that were significantly depleted among MS patients, many of which were associated with cytomegalovirus (CMV). By generating a library of myelin-reactive TCRs from stimulated peripheral blood mononuclear cells (PBMCs) obtained from MS patients and mapping these sequences to the public TCR repertoire database, we also uncovered a lower frequency of myelin-reactive TCRs in MS samples compared to controls in the public datasets. In addition, epitope-specificity prediction revealed a broader response to EBV-, but not CMV-derived epitopes. Collectively, these findings underscore the complex role of chronic viral infections in MS. Particularly, they suggest that EBV-specific immune responses contribute to the dysregulation of the immune system in MS patients, potentially through mechanisms of molecular mimicry. While the broader response to EBV-derived epitopes and the lower frequency of myelin-reactive TCRs in MS samples are both associated with the disease, further research is needed to clarify the nature of this relationship. These observations suggest that viral and autoimmune mechanisms may contribute independently or interact in MS pathogenesis.

immunology↗

bioRxiv2023

Global nuclear reorganization during heterochromatin replication in the giant-genome plant Nigella damascena L.

Among flowering plants, genome size varies remarkably, by >2200-fold, and this variation depends on the loss and gain of non-coding DNA sequences that form distinct heterochromatin complexes during interphase. In plants with giant genomes, most chromatin remains condensed during interphase, forming a dense network of heterochromatin threads called interphase chromonemata. Using super-resolution light and electron microscopy, we studied the ultrastructure of chromonemata during and after replication in root meristem nuclei of Nigella damascena L. During S-phase, heterochromatin undergoes transient decondensation locally at DNA replication sites. Due to the abundance of heterochromatin, the replication leads to a robust disassembly of the chromonema meshwork and a general reorganization of the nuclear morphology visible even by conventional light microscopy. After replication, heterochromatin recondenses, restoring the chromonema structure. Thus, we show that heterochromatin replication in interphase nuclei of giant-genome plants induces a global nuclear reorganization.

cell biology↗