Morphodynamics of T-lymphocytes: Scanning to spreading.

Biophys J

Aix-Marseille Université, CNRS, INSERM, LAI, Turing Centre for Living Systems, Marseille, France. Electronic address:

Published: August 2024

Binding of the T cell receptor complex to its ligand, the subsequent molecular rearrangement, and the concomitant cell-scale shape changes represent the very first steps of adaptive immune recognition. The first minutes of the interaction of T cells and antigen presenting cells have been extensively scrutinized; yet, gaps remain in our understanding of how the biophysical properties of the environment may impact the sequence of events. In particular, many pioneering experiments were done on immobilized ligands and gave major insights into the process of T cell activation, whereas later experiments have indicated that ligand mobility was of paramount importance, especially to enable the formation of T cell receptor clusters. Systematic experiments to compare and reconcile the two schools are still lacking. Furthermore, recent investigations using compliant substrates have elucidated other intriguing aspects of T cell mechanics. Here we review experiments on interaction of T cells with planar artificial antigen presenting cells to explore the impact of mechanics on adhesion and actin morphodynamics during the spreading process. We enumerate a sequence tracing first contact to final spread state that is consistent with current understanding. Finally, we interpret the presented experimental results in light of a mechanical model that captures all the different morphodynamic states.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11331044PMC
http://dx.doi.org/10.1016/j.bpj.2024.02.023DOI Listing

Publication Analysis

Top Keywords

t cell receptor
8
interaction t cells
8
antigen presenting
8
presenting cells
8
morphodynamics t-lymphocytes
4
t-lymphocytes scanning
4
scanning spreading
4
spreading binding
4
t cell
4
binding t cell
4

Similar Publications

Inhibition of aortic CX3CR1+ macrophages mitigates thoracic aortic aneurysm progression in Marfan syndrome in mice.

J Clin Invest

January 2025

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, China.

The pathogenesis of thoracic aortic aneurysm (TAA) in Marfan syndrome (MFS) is generally attributed to vascular smooth muscle cell (VSMC) pathologies. However, the role of immune cell-mediated inflammation remains elusive. Single-cell RNA sequencing identified a subset of CX3CR1+ macrophages mainly located in the intima in the aortic roots and ascending aortas of Fbn1C1041G/+ mice, further validated in MFS patients.

View Article and Find Full Text PDF

Generation of high avidity T cell receptors (TCRs) reactive to tumor-associated antigens (TAA) is impaired by tolerance mechanisms, which is an obstacle to effective T cell therapies for cancer treatment. NY-ESO-1, a human cancer-testis antigen, represents an attractive target for such therapies due to its broad expression in different cancer types and the restricted expression in normal tissues. Utilizing transgenic mice with a diverse human TCR repertoire, we isolated effective TCRs against NY-ESO-1 restricted to HLA-A*02:01.

View Article and Find Full Text PDF

Understanding the Preclinical Efficacy of Antibody-Drug Conjugates.

Int J Mol Sci

November 2024

Experimental Therapeutics Unit, Oncology Department, Hospital Clínico San Carlos (HCSC), Instituto de Investigación Sanitaria San Carlos (IdISSC), 28040 Madrid, Spain.

Antibody-drug conjugates (ADCs) represent a therapeutic modality that guides chemotherapies to tumoral cells by using antibodies against tumor-associated antigens (TAAs). The antibody and the chemotherapy or payload are attached by a chemical structure called the linker. The strategy for the development of this type of drug was based on several rational pillars, including the use of a very potent payload and the use of specific antibodies acting only on antigens expressed on tumoral cells.

View Article and Find Full Text PDF

A devasting stage of chronic hepatic dysfunction is strictly correlated with neurological impairment, signifying hepatic encephalopathy (HE). HE is a multifactorial condition; therefore, hyperammonemia, oxidative stress, neuroinflammation, and mitochondrial dysfunction interplay in HE's progressive development. Cilostazol (Cilo) has shown promising neuroprotective and hepatoprotective effectiveness in different neuronal and hepatic disorders; however, its efficiency against HE hasn't yet been explored.

View Article and Find Full Text PDF

EGFR and MUC1 as dual-TAA drug targets for lung cancer and colorectal cancer.

Front Oncol

November 2024

Department of Tumor Biobank, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China.

Background: Epidermal growth factor receptor (EGFR) is a key protein in cellular signaling that is overexpressed in many human cancers, making it a compelling therapeutic target. On-target severe skin toxicity has limited its clinical application. Dual-targeting therapy represents a novel approach to overcome the challenges of EGFR-targeted therapies.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!