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Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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At least 163 records · Page 9Linked to original sources

bioRxiv2019

Imaging Membrane Curvature inside a Model Immunological Synapse in RBL-2H3 Cells using TIRF Microscopy with Polarized Excitation

Total internal reflection fluorescence microscopy with polarized excitation (P-TIRF) can be used to image nanoscale curvature phenomena in live cells. We used P-TIRF to visualize rat basophilic leukemia cells (RBL-2H3 cells) coming into contact with a supported lipid bilayer, modeling an immunological synapse. These studies help correlate the dynamics of cell surface molecules with the mechanical properties of the plasma membrane during synapse formation.

biophysics↗

bioRxiv2025

Ensemble-DeepSets: an interpretable deep learning framework for single-cell resolution profiling of immunological aging

Immunosenescence increases susceptibility to infection and reduces vaccine responsiveness, yet bulk transcriptomic clocks obscure the cellular heterogeneity underlying this process. Here, we present IDEAL-Age, an interpretable deep learning framework that operates directly on single-cell PBMC transcriptomes. Benchmarking against 31 methods across independent cohorts demonstrates superior predictive performance. The frameworks interpretability uncovers linear and non-linear transcriptomic dynamics that reveal phase-specific physiological transitions, and identifies pro-youthful or pro-aging cellular contributions. Application to systemic lupus erythematosus (SLE) reveals accelerated immunological aging driven by interferon-associated monocyte shifts. IDEAL-Age establishes a high-resolution computational framework for deciphering systemic immune aging.

bioinformatics↗

bioRxiv2026

Synthetic Immunological Niche Reveals Early Immune Dysregulationand Stratifies Therapeutic Response in Type 1 Diabetes

In Type 1 Diabetes (T1D), disease onset and response to immunotherapy vary widely among individuals, reflecting heterogeneous stage-specific immune dysregulation that remains undefined. To investigate this heterogeneity, we engineered a microporous polycaprolactone scaffold that forms a synthetic immunological niche (IN) upon subcutaneous implantation, enabling in vivo capture of systemic immune dysregulation. In non-obese diabetic (NOD) mice, longitudinal transcriptomic profiling of IN-infiltrating cells identified early-stage genes relatively enriched for myeloid cells, followed by progressive increases in T cell-associated dysregulation at later stages that distinguished T1D progressors from non-progressors. We derived an early-stage IN-based T1D gene signature capturing immune alterations. The signature stratified NOD progressors from non-progressors as early as 6 weeks of age and was conserved across human T1D datasets, distinguishing T1D from non-diabetic individuals in spleen and pancreatic lymph node samples, but not peripheral blood. Signature-based stratification further revealed enrichment of macrophage-associated TNF- pathways in NOD progressors, validated in human T1D islets. Given heterogeneous response to anti-TNF- therapy, IN profiling identified resistance-associated mechanisms and enabled derivation of a pathway score that prospectively distinguished treatment-sensitive from resistant mice prior to therapy, establishing the IN as a minimally invasive platform for detecting stage-wise immune dysregulation and stratifying immunotherapy response in T1D.

bioengineering↗

bioRxiv2026

From mice to humans: A multi-omic predictive framework for translational immunology

Mice are key preclinical animal models in vaccine and immunological research, yet their predictive value for human immunity remains contested. Here, we evaluated the translatability of murine models across inactivated and subunit vaccination (influenza, hepatitis B), acute infection (S. aureus, E. coli), and injury (burns and trauma), integrating transcriptomic profiles with sequence evolution, cis-regulatory architecture, and functional annotation. Functional modules were more conserved between species than individual orthologous genes. Translational accuracy depended on stimulus intensity, as infections and injuries engaged conserved signatures, while single-dose vaccination diverged. We then built multilayer models to predict human expression rank and direction of change, and to classify shared leading-edge genes. Adding evolutionary and regulatory layers improved these predictions. We provide a step-by-step R Markdown notebook to apply the models to user data. The study code and datasets are available at https://github.com/wapsyed/mousetohuman_multilayer

bioinformatics↗

bioRxiv2014

The immunologic V-gene repertoire in mammals

From recent whole genome shotgun data of 48 mammalian species, we have used our software VgenExtractor to obtain the functional V-gene sequence repertoire in order to conduct comparative phylogenetic studies. These studies reveal a large variation in the number of V-genes across mammalian species, ranging from a mere 36 V-genes in dolphins to nearly 600 V-genes in rats. Monotremes and marsupials are the only mammals possessing an additional locus, the TRMV, apart from the seven common loci found in mammals. Also, we show evidence for the loss of the light chain loci, specifically the V{kappa} chain in one microbat, and the V{lambda} chain in one rodent species. Finally, we suggest different features related to the evolution of immunoglobulin and T cell receptor loci, where frequent sequence duplications are seen in the former, while preserved and undiversified lineages are observed in the latter. All the V-gene sequences described in this study are available in the public database repository vgenerepertoire.org.

Immunology↗

bioRxiv2014

The whole diagram of the discovered host immunological pathways

Tfh initiates four eradicable immunities. Tfh includes FDC, LTi, IL21 CD4 T cell, and IgG/M B cell. Treg initiates four tolerable immunities. Treg includes DCreg, ILCreg, TGF{beta} CD4 T cell, and IgA B cell. TH1/TH1-like is immunity for intracellular bacteria/protozoa and type 4 delayed type hypersensitivity. TH1 includes M1 macrophage, mDC2, Tc1 CD8 T cell, IFNg CD4 T cell, ILC1, iNKT1, and IgG3 B cell. TH1-like includes M2 macrophage, ILC1, suppressive CD8 T cell, IFNg/TGF{beta} CD4 T cell, regulatory iNKT cells, and IgA1 B cell. TH2/TH9 is immunity for helminths and type1 IgE mediated hypersensitivity. TH2 includes iEOS eosinophil, Langerhans cell, basophil/MCt mast cell, IL-4 CD4 T cell, ILC2, iNKT2, and IgE/IgG4 B cell. TH9 includes rEOS eosinophil, basophils/mast cell MCct, IL-9 CD4 T cell, ILC2, regulatory iNKT cells, and IgA2 B cell. TH22/TH17 is immunity for extracellular bacteria/fungi and type 3 immune complex hypersensitivity. TH22 includes N1 neutrophils, mDC1, IL-22 CD4 T cell, ILC3(NCR+), iNKT17, and IgG2 B cell. TH17 includes N2 neutrophils, IL-17 CD4 T cell, regulatory iNKT cells, ILC3(NCR-), and IgA2 B cell. TH{beta}/TH3 is immunity for viruses and type 2 antibody dependent cytotoxic hypersensitivity. TH{beta} includes NK1 natural killer cell, pDC, Tc2 CD8 T cell, IL10 CD4 T cell, ILC10, iNKT10, and IgG1 B cell. TH3 includes NK2 natural killer cell, suppressive CD8 T cell, ILC10, IL-10/TGF{beta} CD4 T cell, regulatory iNKT cells, and IgA1 B cell. Summary sentenceThe summarized framework of host immunities to explain their relations to specific pathogens and hypersensitivities

Immunology↗

bioRxiv2016

Immunological Patterns from Four Melioidosis Cases: Constant and Variable Protein Antigens

Burkholderia pseudomallei is the causative agent of the melioidosis and is endemic to Southeast Asia and northern Australia. There is no available vaccine and accurate diagnosis is difficult, time-consuming and labor intensive. Early diagnosis is an important part of successful treatment and current serological tests are inadequate and based upon multiple antigens. Identifying specific immunogenic proteins which are highly seroreactive may yield potential diagnostic targets for detecting antibodies and antigens specific to melioidosis. We have used 2D gel electrophoresis and Western blotting analysis to analyze protein antigenicity of whole cell lysates extracted from four B. pseudomallei strains and the sera from the specific infected humans. We found a total of 135 immunogenic proteins, 62 of which we were able to identify to a specific gene by mass-spectrometry. Results from the Western blotting of each strains proteins and the corresponding patient serum reveal between 30 - 40% serum x strain specific immunogenic proteins. In most cases, these differences exist despite the fact that the genes encoding these proteins were present among all four B. pseudomallei strains. Eight particular proteins were immunogenic in all four strain x serum combinations and could represent novel diagnostic and vaccine subunit targets.

immunology↗

bioRxiv2016

Two-zone tumor tolerance can arise from a simple immunological feedforward motif that estimates tumor growth rates

Since the early 1990s, many authors have independently suggested that self/nonself recognition by the immune system might be modulated by the rates of change of antigen challenges. This paper introduces an extremely simple and purely conceptual mathematical model that allows dynamic discrimination of immune challenges. The main component of the model is a motif which is ubiquitous in systems biology, the incoherent feedforward loop, which endows the system with the capability to estimate exponential growth exponents, a prediction which is consistent with experimental work showing that exponentially increasing antigen stimulation is a determinant of immune reactivity. Combined with a bistable system and a simple feedback repression mechanism, an interesting phenomenon emerges as a tumor growth rate increases: elimination, tolerance (tumor growth), again elimination, and finally a second zone of tolerance (tumor escape). This prediction from our model is analogous to the \"two-zone tumor tolerance\" phenomenon experimentally validated since the mid 1970s. Moreover, we provide a plausible biological instantiation of our circuit using combinations of regulatory and effector T cells.

immunology↗

bioRxiv2017

c-Maf-dependent regulatory T cells mediate immunological tolerance to intestinal microbiota

Both microbial and host genetic factors contribute to the pathogenesis of autoimmune disease1-4. Accumulating evidence suggests that microbial species that potentiate chronic inflammation, as in inflammatory bowel disease (IBD), often also colonize healthy individuals. These microbes, including the Helicobacter species, have the propensity to induce autoreactive T cells and are collectively referred to as pathobionts4-8. However, an understanding of how such T cells are constrained in healthy individuals is lacking. Here we report that host tolerance to a potentially pathogenic bacterium, Helicobacter hepaticus (H. hepaticus), is mediated by induction of ROR{gamma}t+Foxp3+ regulatory T cells (iTreg) that selectively restrain pro-inflammatory TH17 cells and whose function is dependent on the transcription factor c-Maf. Whereas H. hepaticus colonization of wild-type mice promoted differentiation of ROR{gamma}t-expressing microbe-specific iTreg in the large intestine, in disease-susceptible IL-10-deficient animals there was instead expansion of colitogenic TH17 cells. Inactivation of c-Maf in the Treg compartment likewise impaired differentiation of bacteria-specific iTreg, resulting in accumulation of H. hepaticus-specific inflammatory TH17 cells and spontaneous colitis. In contrast, ROR{gamma}t inactivation in Treg only had a minor effect on bacterial-specific Treg-TH17 balance, and did not result in inflammation. Our results suggest that pathobiont-dependent IBD is a consequence of microbiota-reactive T cells that have escaped this c-Maf-dependent mechanism of iTreg-TH17 homeostasis.

immunology↗

bioRxiv2020

Interrupting reactivation of immunological memory reprograms allergy and averts anaphylaxis

IgE production against innocuous antigens can lead to life-threatening reactions such as anaphylaxis. While IgE levels drastically decline with strict allergen avoidance, the ability to regenerate IgE can persist for a lifetime, as is the case for peanut allergy. The mechanism by which IgE regenerates remains unresolved. A novel culture system and application of single-cell RNA-sequencing, elucidated the transcriptomic signature of human peanut-reactive B and T cells and revealed IL-4/IL-13 as a signaling pathway critical for the IgE recall response. Indeed, interruption of this pathway not only prevented IgE production and anaphylaxis, but also reprogrammed the pathogenic response against peanut. This investigation advances our understanding of the mechanism that regenerates IgE in food allergy and spotlights IL-4/IL-13 blockade as a therapeutic with disease-transforming potential. One Sentence SummarySingle-cell transcriptomics of allergic memory responses reveals how to teach the immune system to forget.

immunology↗

bioRxiv2020

Single-cell landscape of immunological responses in COVID-19 patients

In COVID-19 caused by SARS-CoV-2 infection, the relationship between disease severity and the host immune response is not fully understood. Here we performed single-cell RNA sequencing in peripheral blood samples of five healthy donors and 13 COVID-19 patients including moderate, severe and convalescent cases. Through determining the transcriptional profiles of immune cells, coupled with assembled T cell receptor and B cell receptor sequences, we analyzed the functional properties of immune cells. Most cell types in COVID-19 patients showed a strong interferon-alpha response, and an overall acute inflammatory response. Moreover, intensive expansion of highly cytotoxic effector T cell subsets, such as CD4+ Effector-GNLY (Granulysin), CD8+ Effector-GNLY and NKT CD160, was associated with convalescence in moderate patients. In severe patients, the immune landscape featured a deranged interferon response, profound immune exhaustion with skewed T cell receptor repertoire and broad T cell expansion. These findings illustrate the dynamic nature of immune responses during the disease progression.

immunology↗

bioRxiv2020

Coformulation with tattoo ink for immunological assessment of vaccine immunogenicity in the draining lymph node

Characterisation of germinal centre B and T cell responses yields critical insights into vaccine immunogenicity. Non-human primates are a key pre-clinical animal model for human vaccine development, allowing both lymph node and circulating immune responses to be longitudinally sampled for correlates of vaccine efficacy. However, patterns of vaccine antigen drainage via the lymphatics after intramuscular immunisation can be stochastic, driving uneven deposition between lymphoid sites, and between individual lymph nodes within larger clusters. In order to improve the accurate isolation of antigen-exposed lymph nodes during biopsies and necropsies, we developed and validated a method for co-formulating candidate vaccines with tattoo ink, which allows for direct visual identification of vaccine-draining lymph nodes and evaluation of relevant antigen-specific B and T cell responses by flow cytometry. This approach improves the assessment of vaccine-induced immunity in highly relevant non-human primate models.

immunology↗

bioRxiv2020

Cold Exposure Protects from Neuroinflammation Through Immunologic Reprogramming

Autoimmunity is energetically costly, but the impact of a metabolically active state on immunity and immune-mediated diseases is unclear. Ly6Chi monocytes are key effectors in CNS autoimmunity with elusive role in priming naive autoreactive T cells. Here we provide unbiased analysis of the immune changes in various compartments during cold exposure, and show that this energetically costly stimulus markedly ameliorates active experimental autoimmune encephalomyelitis (EAE). Cold exposure decreases MHCII on monocytes at steady-state and in various inflammatory mouse models, and suppresses T cell priming and pathogenicity through the modulation of monocytes. Genetic, or antibody-mediated monocyte depletion, or adoptive transfer of Th1- or Th17-polarized cells for EAE abolish the cold-induced effects on T cells or EAE, respectively. These findings provide a mechanistic link between environmental temperature and neuroinflammation, and suggest competition between cold-induced metabolic adaptations and autoimmunity as energetic trade-off beneficial for the immune-mediated diseases.

immunology↗

bioRxiv2020

Immunological memory to SARS-CoV-2 assessed for greater than six months after infection

Understanding immune memory to SARS-CoV-2 is critical for improving diagnostics and vaccines, and for assessing the likely future course of the COVID-19 pandemic. We analyzed multiple compartments of circulating immune memory to SARS-CoV-2 in 254 samples from 188 COVID-19 cases, including 43 samples at [≥] 6 months post-infection. IgG to the Spike protein was relatively stable over 6+ months. Spike-specific memory B cells were more abundant at 6 months than at 1 month post symptom onset. SARS-CoV-2-specific CD4+ T cells and CD8+ T cells declined with a half-life of 3-5 months. By studying antibody, memory B cell, CD4+ T cell, and CD8+ T cell memory to SARS-CoV-2 in an integrated manner, we observed that each component of SARS-CoV-2 immune memory exhibited distinct kinetics.

immunology↗

bioRxiv2021

Structural and immunological identification and antiviral infection experiment of the dominant cytotoxic T lymphocyte epitopes of the oncogenic Marek's disease virus

Mareks disease (MD) is a serious cancer caused by MDV in chickens, and it is also the first tumor disease that could be controlled by an attenuated vaccine in the world. However, the attenuated vaccine is able to inhibit only the formation of tumors but cannot prevent the infection of oncogenic viruses; instead, it leads to mutations and the emergence of a number of virulent strains. In this paper, the crystal structures of chicken MHC class I (pBF2*1501) molecules bound with 8-mer and 9-mer MDV peptides were solved. The results showed that the conformations of the 8-mer and 9-mer peptides in the antigen-binding groove (ABG) of pBF2*1501 are different; the ABG-8-mer is flat, and the ABG-9-mer has the "featured" M-type epitope morphology. Based on these results, multiple MDV epitopes were confirmed using the tetramer technique, and the immunoprotective effect of dominant epitope was confirmed using the protein adjuvant HSP108-N333 in BF2*1501-expressing chickens. The results showed that the two epitopes have obvious protective effects after a standard immunization program. After challenge, the mortality rate was only 20%, and the protective index (PI) reached 33% in the epitope group. The results verified that a single epitope could induce extremely strong specific antitumor T lymphocyte immunity. The results show that three key factors are crucial to obtain the best antitumor effect: accurate identification of dominant cytotoxic T lymphocyte (CTL) epitopes, efficient protein adjuvant and MHC matching. Meanwhile, the results also provided obvious advantages for the development of multiple epitope vaccines for tumor diseases. ImportanceMareks disease (MD) is the first tumor disease that can be controlled by an attenuated vaccine. However, the attenuated vaccine cannot prevent the infection of the oncogenic virus and instead leads to the emergence of a number of mutated virulent strains. First, the mechanism of the chicken BF2*1501 preferentially presents 9-mer peptide was clarified. Based on this result, multiple MDV epitopes were confirmed, and the dominant epitopes were identified. Subsequently, two epitope groups showed obvious protective effects after a standard immunization program, and the protective index (PI) of one of the epitope groups reached over 30%. The results showed that a single epitope could induce strong and efficient antitumor CTL immunity. Overall, three key factors are crucial to obtain the best antitumor effect: accurate identification of dominant epitopes, efficient protein adjuvant and MHC matching. Our results provide an obvious strategy for the development of multiple epitope vaccines in tumor diseases.

immunology↗

bioRxiv2021

The dilemma of infection versus colonization at mucosal tissues: immunological and bacteriological features of obstructive tonsillar hypertrophy

Immune responses at the boundary between the host and the world beyond are complex and mucosal tissue homeostasis relies on them. Obstructive sleep apnea (OSA) is a syndrome suffered by children with hypertrophied tonsils. We uncovered a crucial role of pro-inflammatory tonsillar B and T cells in sustaining hypertrophy and hyperplasia by producing TNF and IL17, respectively. We detected prominent levels of expression of CD1d by tonsillar stratified as well as reticular epithelium, which have not previously been reported. By combining bacterial culture from the tonsillar core and subsequent identification of the respective isolates, we determined the most prevalent species within the cohort of OSA patients. Although the isolated species are considered normal oropharyngeal commensals in children, we confirmed their capacity to breach the epithelial barrier. Our work shed light on the pathological mechanism underlying OSA, highlighting the relevance taken by the host immune system when defining infection versus colonization.

immunology↗

bioRxiv2021

Longitudinal single-cell epitope and RNA-sequencing reveals the immunological impact of type 1 interferon autoantibodies in critical COVID-19

Type I interferon (IFN-I) neutralizing autoantibodies have been found in some critical COVID-19 patients; however, their prevalence and longitudinal dynamics across the disease severity scale, and functional effects on circulating leukocytes remain unknown. Here, in 284 COVID-19 patients, we found IFN-I autoantibodies in 19% of critical, 6% of severe and none of the moderate cases. Longitudinal profiling of over 600,000 peripheral blood mononuclear cells using multiplexed single-cell epitope and transcriptome sequencing from 54 COVID-19 patients, 15 non-COVID-19 patients and 11 non-hospitalized healthy controls, revealed a lack of IFN-I stimulated gene (ISG-I) response in myeloid cells from critical cases, including those producing anti-IFN-I autoantibodies. Moreover, surface protein analysis showed an inverse correlation of the inhibitory receptor LAIR-1 with ISG-I expression response early in the disease course. This aberrant ISG-I response in critical patients with and without IFN-I autoantibodies, supports a unifying model for disease pathogenesis involving ISG-I suppression via convergent mechanisms.

immunology↗

bioRxiv2021

Immunological features that determine the strength of antibody responses to BNT162b2 mRNA vaccine against SARS-CoV-2

We analyzed peripheral blood mononuclear cells (PBMCs) of each 20 individuals with a high anti-SARS-CoV-2 antibody titer and a low antibody titer out of 1,774 healthcare workers who received BNT162b2 mRNA vaccine. A higher antibody titer was associated with the frequencies of naive and transitional B cells before vaccination. In addition, fold changes in the frequency of activated CD8+ T cells upon vaccination were correlated with the antibody titers.

immunology↗