Biology subjects

Webber, A.

Publications and source records attributed to Webber, A..

4 recordsLinked to original sources

bioRxiv2026

Duration of Initial Viremia Modulates Functional Properties of HIV-specific T Cell Receptors

Virus-specific CD8+ T cells are crucial in controlling chronic human viral infections such as HIV-1, but the effect of persistent antigen exposure on T cell repertoire formation is not well understood. In this study, we examined epitope-specific CD8+ T cell repertoires in people living with HIV-1, where duration of viremia following hyperacute infection was modulated by the time of initiation of continuous suppressive antiretroviral therapy (ART). After ART-induced undetectable viremia in persons expressing the same HLA class I allele, we analyzed the impact of early (n=6) versus delayed (n=6) ART initiation on the clonotypic composition, clonotypic cross-reactivity, functional avidity and memory differentiation profile of the HIV-specific T cell repertoire restricted by HLA-B*58:01. Using a panel of barcoded tetramers, we mapped T cell receptor (TCR) clonotypes specific for three dominant epitopes and their variants. Both groups exhibited polyclonal TCR repertoires with evidence of cross-reactivity, which was significantly enriched in donors with prolonged antigen exposure. Within this cohort, broadly cross-reactive clonotypes capable of recognizing all autologous variants were identified, but these were rare (<1%). Early ART initiation preserved repertoires characterized by higher-avidity TCRs and a relative enrichment of transitional memory CD8+ T cell subsets. These functional differences were not associated with differences in TRBV gene sharing, indicating that ART timing shapes repertoire quality and memory differentiation without altering TRBV gene bias. These findings demonstrate how antigen suppression dynamics differentially shape the breadth, functional sensitivity, and memory composition of the HIV-specific TCR repertoire, with implications for T cell-directed immunotherapies and HIV cure strategies. One Sentence SummaryThe duration of viral antigen exposure during early HIV infection shapes the functional quality, breadth, and memory composition of virus-specific CD8 T cell receptor repertoires. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=77 SRC="FIGDIR/small/702605v1_ufig1.gif" ALT="Figure 1"> View larger version (17K): org.highwire.dtl.DTLVardef@9a5a6dorg.highwire.dtl.DTLVardef@1a6bbdaorg.highwire.dtl.DTLVardef@17707e8org.highwire.dtl.DTLVardef@1a84d9e_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2023

Three-Dimensional Bioconjugated Liquid-Like Solid (LLS) Enhance Characterization of Solid Tumor - Chimeric Antigen Receptor T cell Interactions

Cancer immunotherapy offers lifesaving treatments for cancers, but the lack of reliable preclinical models that could enable the mechanistic studies of tumor-immune interactions hampers the identification of new therapeutic strategies. We hypothesized 3D confined microchannels, formed by interstitial space between bio-conjugated liquid-like solids (LLS), enable CAR T dynamic locomotion within an immunosuppressive TME to carry out anti-tumor function. Murine CD70-specific CAR T cells cocultured with the CD70-expressing glioblastoma and osteosarcoma demonstrated efficient trafficking, infiltration, and killing of cancer cells. The anti-tumor activity was clearly captured via longterm in situ imaging and supported by upregulation of cytokines and chemokines including IFNg, CXCL9, CXCL10, CCL2, CCL3, and CCL4. Interestingly, target cancer cells, upon an immune attack, initiated an "immune escape" response by frantically invading the surrounding microenvironment. This phenomenon however was not observed for the wild-type tumor samples which remained intact and produced no relevant cytokine response. Single cells collection and transcriptomic profiling of CAR T cells at regions of interest revealed feasibility of identifying differential gene expression amongst the immune subpopulations. Complimentary 3D in vitro platforms are necessary to uncover cancer immune biology mechanisms, as emphasized by the significant roles of the TME and its heterogeneity.

bioengineering↗

bioRxiv2019

The impact of the "World's 25 Most Endangered Primates" list on scientific publications and media

Assessing the impact of conservation campaigns is of high importance for optimizing the use of limited resources. Lists of threatened species are often used as media outreach tools, but their usefulness is rarely tested. We investigated whether the inclusion of a species in the list "Worlds 25 Most Endangered Primates", published biannually by the International Primatological Society, the International Union for Conservation of Natures Species Survival Commission Primate Specialist Group, and Conservation International from 2000, had an effect both on scientific publications and on the general public. We analyzed a database of 40 million articles from major scientific publishers (Elsevier, Springer, Nature, Plos, Pubmed, Biomed Central) finding an increase in the number of papers mentioning a species after its inclusion in the list. We also analyzed media penetration (data from Google News), and online interest (data from Google Blogs, Twitter, and Google Trends), collecting daily data for one month before and one after the official launch of the 2014-2016 list (24th November 2015). The results show a short spike of interest on Google News and Twitter but no long term effect, indicating a limited effect on the general public. Our results are important for the understanding of the impact of current conservation campaigns and to provide strategies for future campaigns.

scientific communication and education↗

bioRxiv2018

Cytoarchitecture and Layer Estimation in High-Resolution Neuroanatomical Images

Robust methods for characterizing the cellular architecture (cytoarchitecture) of the brain are needed to differentiate brain areas, identify neurological diseases, and model architectural differences across species. Current methods for mapping the cytoarchitecture and, in particular, identifying laminar (layer) divisions in tissue samples require the expertise of trained neuroanatomists to manually annotate the various regions-of-interest and cells within an image. However, as neuroanatomical datasets grow in volume, manual annotations become inefficient, impractical, and risk the potential of biasing results. In this paper, we propose an automated framework for cellular detection and density estimation that enables the detection of laminar divisions within retinal and neocortical histology datasets. Our approach for layer detection uses total variation minimization to find a small number of change points in the density that signify the beginning and end of each layer. We apply these methods to micron-scale histology images from a variety of cortical areas of the mouse brain and retina, as well as synthetic datasets. Our results demonstrate the feasibility of using automation to reveal the cytoarchitecture of neurological samples in high-resolution images.

neuroscience↗