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Related Concept Videos

T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
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PI3K/mTOR/AKT Signaling Pathway01:22

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The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
B Cell Activation and Differentiation01:24

B Cell Activation and Differentiation

The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Covalently Linked Protein Regulators02:04

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Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.

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Related Experiment Video

Updated: May 21, 2026

Spatial and Temporal Control of T Cell Activation Using a Photoactivatable Agonist
07:48

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Published on: April 25, 2018

Substrate rigidity regulates human T cell activation and proliferation.

Roddy S O'Connor1, Xueli Hao, Keyue Shen

  • 1Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|June 27, 2012
PubMed
Summary
This summary is machine-generated.

Substrate stiffness significantly impacts T cell expansion. Softer surfaces boost T cell activation, proliferation, and differentiation, offering new insights for adoptive immunotherapy development.

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Published on: December 30, 2016

Area of Science:

  • Immunology
  • Biomaterials Science
  • Cell Biology

Background:

  • Adoptive immunotherapy relies on cultured T cells for treating cancer and infectious diseases.
  • Current T cell culture often uses stiff polystyrene surfaces, potentially overlooking mechanical influences.
  • Substrate mechanics are known to affect other cell types like stem cells and fibroblasts.

Purpose of the Study:

  • To investigate the effect of culture substrate stiffness on human T cell activation and expansion ex vivo.
  • To determine if varying substrate rigidity influences key T cell responses like proliferation and cytokine production.

Main Methods:

  • Developed a system using poly(dimethylsiloxane) substrates with tunable rigidity.
  • Stimulated T cells via the T cell receptor (TCR)/CD3 complex and CD28 co-stimulatory receptor.
  • Measured IL-2 production, cell proliferation, and differentiation markers (CD62L, IFN-γ) across different substrate stiffnesses.

Main Results:

  • Softer substrates (Young's Modulus < 100 kPa) promoted a 4-fold increase in IL-2 production and proliferation for CD4(+) and CD8(+) T cells compared to stiffer substrates (> 2 MPa).
  • A trend towards increased effector-differentiated (CD62L negative) T cells was observed on stiffer substrates, though not statistically significant.
  • Naive CD4(+) T cells expanded on softer substrates showed a 3-fold higher proportion of IFN-γ-producing Th1-like cells.

Conclusions:

  • Substrate rigidity is a critical, previously unrecognized factor influencing T cell activation, proliferation, and differentiation.
  • Softer biomaterials enhance T cell responses, suggesting their utility in optimizing T cell culture for immunotherapy.
  • Consideration of substrate mechanical properties is essential for designing effective T cell culture systems and interpreting experimental results.