Mechanobiology of antigen‐induced T cell arrest

Chabaud, Mélanie; Paillon, Noémie; Gaus, Katharina; Hivroz, Claire

doi:10.1111/boc.201900093

Cited by 8 publications

(5 citation statements)

References 136 publications

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“…Each block contains a multi-head attention layer and a fully connected feedforward network, in which the multi-head attention mechanism is the core part of the overall framework, helping the model to grasp the information contained by the individual amino acids in the sequence and their relationships to each other. The attention score of a single head can be calculated using formula (1), where Q represents Query, K represents Key, V represents Value and dk represents the dimensionality of the Key. Attention(Q,K,V)=softmax(…”

Section: Overview Of Gratcrmentioning

confidence: 99%

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GRATCR: epitope-specific T cell receptor sequence generation with data-efficient pre-trained models

Zhou,

Chen,

Lin

et al. 2024

Preprint

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T cell receptors (TCRs) play a crucial role in numerous immunotherapies targeting tumor cells. However, their acquisition and optimization present significant challenges, involving laborious and time-consuming wet lab experimental resource. Deep generative model has demonstrated remarkable capabilities in functional protein sequence generation, offering a promising solution for enhancing the acquisition of specific TCR sequences. Here, we propose GRATCR, a framework incorporates two pre-trained modules through a novel "grafting" strategy, to de-novo generate TCR sequences targeting specific epitopes. Experimental results demonstrate that TCRs generated by GRATCR exhibit higher specificity toward desired epitopes and are more biologically functional compared with state-of-the-art model, by using significantly fewer training data. Additionally, the generated sequences display novelty compared to natural sequences, and the interpretability evaluation further confirmed that the model is capable of capturing important binding patterns. GRATCR is freely available at https://github.com/zhzhou23/GRATCR.

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Section: Overview Of Gratcrmentioning

confidence: 99%

“…T cells, an integral part of the immune system, play a pivotal role in adaptive immunity by recognizing a diverse range of antigens [1,2]. This recognition is facilitated by the T cell receptor (TCR), a specialized cell surface protein crucial for antigen recognition and T cell activation [3].…”

Section: Introductionmentioning

confidence: 99%

GRATCR: epitope-specific T cell receptor sequence generation with data-efficient pre-trained models

Zhou,

Chen,

Lin

et al. 2024

Preprint

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“…A prerequisite to load distribution would be the physical coupling of the involved surface area. Along this line of reasoning, the biophysical parameters of membrane curvature and tension recently emerged as a possible mechanism influencing T-cell motility, protrusion, and immune synapse formation (reviewed in ( 126 )). The decisive physical parameter in this model is the modulation of membrane tension and tension decay at the triggering point, which could even be used to explain certain aspects of ligand discrimination ( 127 ) and synapse breaking ( 128 ).…”

Section: Mechanical Forces In T-cell Antigen Recognitionmentioning

confidence: 99%

Mechanosurveillance: Tiptoeing T Cells

et al. 2022

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Efficient scanning of tissue that T cells encounter during their migratory life is pivotal to protective adaptive immunity. In fact, T cells can detect even a single antigenic peptide/MHC complex (pMHC) among thousands of structurally similar yet non-stimulatory endogenous pMHCs on the surface of antigen-presenting cells (APCs) or target cells. Of note, the glycocalyx of target cells, being composed of proteoglycans and bulky proteins, is bound to affect and even modulate antigen recognition by posing as a physical barrier. T cell-resident microvilli are actin-rich membrane protrusions that puncture through such barriers and thereby actively place the considerably smaller T-cell antigen receptors (TCRs) in close enough proximity to APC-presented pMHCs so that productive interactions may occur efficiently yet under force. We here review our current understanding of how the plasticity of T-cell microvilli and physicochemical properties of the glycocalyx may affect early events in T-cell activation. We assess insights gained from studies on T-cell plasma membrane ultrastructure and provide an update on current efforts to integrate biophysical aspects such as the amplitude and directionality of TCR-imposed mechanical forces and the distribution and lateral mobility of plasma membrane-resident signaling molecules into a more comprehensive view on sensitized T-cell antigen recognition.

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“…Cell biological investigation of T cells derived from the immunodeficiency diseases has further led to insights into the roles of F-actin organizations at the immunological synapse. The results from these investigations have shown that polymerization of fresh filamentous actin (Factin) as well as F-actin remodeling assist various stages of synapse: in T cell migration, in formation of immunological synapse, in signaling at immunological synapse, as well as in regulating synapse duration (Chabaud et al, 2020;Colin-York et al, 2019a;Colin-York et al, 2019b;Comrie and Burkhardt, 2016;Kumari et al, 2013). At the immunological synapse, the spreading of T cell lamellae via cortical actin polymerization assists in increasing the surface contact area of a T cell with the antigen presenting cell (APC) to bolster antigen recognition.…”

Section: A U T H O R Accepted Manuscript Author Accepted Manuscriptmentioning

confidence: 99%

Morphological Definition of Actin Architecture at the T Cell Immunological Synapse

Kumari

Irvine

2021

J Indian Inst Sci

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T lymphocytes (T cells) are the major mediators of adaptive immune response. They detect pathogens primarily via the interaction of their T cell receptor (TCR) with the cognate pathogenderived peptide displayed in the context of MHC on the infected cell. A critical step in T cell activation is formation of immunological synapse, a specialized cell-cell conjugate interface between the T cell and infected cell, where massive TCR-induced actin remodeling and polymerization takes place. Dynamic actin polymerization at the immunological synapse is essential for T cell activation and subsequently, immune response.

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Mechanobiology of antigen‐induced T cell arrest

Cited by 8 publications

References 136 publications

GRATCR: epitope-specific T cell receptor sequence generation with data-efficient pre-trained models

GRATCR: epitope-specific T cell receptor sequence generation with data-efficient pre-trained models

Mechanosurveillance: Tiptoeing T Cells

Morphological Definition of Actin Architecture at the T Cell Immunological Synapse

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