Mechanistic and Statistical Modeling Approaches to Study Alloimmune T-cell responses

Editorial

16 April 2025

Editorial: Mechanistic and statistical modeling approaches to study alloimmune T-cell responses

Mario Castro

Josep Bassaganya-Riera

and

Miguel Fribourg

127 views

0 citations

Editors

Miguel Fribourg

Icahn School of Medicine at Mount Sinai

Mario Castro

Comillas Pontifical University

Josep Bassaganya-Riera

Landos Biopharma, Inc.

Impact

Review

01 March 2024

Asymmetric T-cell division: insights from cutting-edge experimental techniques and implications for immunotherapy

Yaroslav Kaminskiy

, 3 more and

Emil Bulatov

T cell can divide asymmetrically after the activation by APC showing unequal distribution of various proteins between proximal and distal daughters. Proximal and distal daughters are prone to become effector and memory T cells respectively. APC, antigen-presenting cell.

Asymmetric cell division is a fundamental process conserved throughout evolution, employed by both prokaryotic and eukaryotic organisms. Its significance lies in its ability to govern cell fate and facilitate the generation of diverse cell types. Therefore, attaining a detailed mechanistic understanding of asymmetric cell division becomes essential for unraveling the complexities of cell fate determination in both healthy and pathological conditions. However, the role of asymmetric division in T-cell biology has only recently been unveiled. Here, we provide an overview of the T-cell asymmetric division field with the particular emphasis on experimental methods and models with the aim to guide the researchers in the selection of appropriate in vitro/in vivo models to study asymmetric division in T cells. We present a comprehensive investigation into the mechanisms governing the asymmetric division in various T-cell subsets underscoring the importance of the asymmetry in fate-determining factor segregation and transcriptional and epigenetic regulation. Furthermore, the intricate interplay of T-cell receptor signaling and the asymmetric division geometry are explored, shedding light on the spatial organization and the impact on cellular fate.

4,029 views

3 citations

Original Research

17 April 2024

Mathematical modeling of endogenous and exogenously administered T cell recirculation in mouse and its application to pharmacokinetic studies of cell therapies

Antonina Nikitich

, 2 more and

Gennady Bocharov

2,593 views

0 citations

Review

13 September 2023

Pre-organized landscape of T cell surface

Yunmin Jung

T cell activation is initiated by the recognition of specific antigenic peptides and subsequently accomplished by complex signaling cascades. These aspects have been extensively studied for decades as pivotal factors in the establishment of adaptive immunity. However, how receptors or signaling molecules are organized in the resting state prior to encountering antigens has received less attention. Recent advancements in super-resolution microscopy techniques have revealed topographically controlled pre-formed organization of key molecules involved in antigen recognition and signal transduction on microvillar projections of T cells before activation and substantial effort has been dedicated to characterizing the topological structure of resting T cells over the past decade. This review will summarize our current understanding of how key surface receptors are pre-organized on the T-cell plasma membrane and discuss the potential role of these receptors, which are preassembled prior to ligand binding in the early activation events of T cells.

2,930 views

6 citations

Original Research

10 January 2024

Identification and validation of platelet-related diagnostic markers and potential drug screening in ischemic stroke by integrating comprehensive bioinformatics analysis and machine learning

Yifei Geng

, 5 more and

Xiaobo Sun

3,409 views

1 citations

Methods

07 July 2023

NAIR: Network Analysis of Immune Repertoire

Hai Yang

, 4 more and

Li Zhang

T cells represent a crucial component of the adaptive immune system and mediate anti-tumoral immunity as well as protection against infections, including respiratory viruses such as SARS-CoV-2. Next-generation sequencing of the T-cell receptors (TCRs) can be used to profile the T-cell repertoire. We developed a customized pipeline for Network Analysis of Immune Repertoire (NAIR) with advanced statistical methods to characterize and investigate changes in the landscape of TCR sequences. We first performed network analysis on the TCR sequence data based on sequence similarity. We then quantified the repertoire network by network properties and correlated it with clinical outcomes of interest. In addition, we identified (1) disease-specific/associated clusters and (2) shared clusters across samples based on our customized search algorithms and assessed their relationship with clinical outcomes such as recovery from COVID-19 infection. Furthermore, to identify disease-specific TCRs, we introduced a new metric that incorporates the clonal generation probability and the clonal abundance by using the Bayes factor to filter out the false positives. TCR-seq data from COVID-19 subjects and healthy donors were used to illustrate that the proposed approach to analyzing the network architecture of the immune repertoire can reveal potential disease-specific TCRs responsible for the immune response to infection.