Related Experiment Video

Updated: Aug 14, 2026

Static Adhesion Assay for the Study of Integrin Activation in T Lymphocytes
09:14

Static Adhesion Assay for the Study of Integrin Activation in T Lymphocytes

Published on: June 13, 2014

PD-L2:PD-1 involvement in T cell proliferation, cytokine production, and integrin-mediated adhesion

Paul A Saunders1, Vana R Hendrycks, William A Lidinsky

  • 1Bioassay Department, R&D Systems, Inc., Minneapolis, MN 55413, USA.

European Journal of Immunology
|November 10, 2005
PubMed

Insights

Programmed death ligand 2 (PD-L2) negatively regulates human T cell activity, inhibiting proliferation and cytokine production through programmed death-1 (PD-1). PD-1 also inhibits integrin-mediated adhesion, involving SHP-2 phosphatase activity.

Area of Science:

  • Immunology
  • Cell Biology

Background:

  • The B7 family member programmed death ligand 2 (PD-L2) has been linked to T cell regulation.
  • Its precise role in human T cell function requires further elucidation.

Purpose of the Study:

  • To investigate the function of PD-L2 on human T cells.
  • To elucidate the molecular mechanisms underlying PD-L2-mediated T cell modulation.

Main Methods:

  • Human T cells were stimulated with anti-CD3 mAb with or without PD-L2.
  • T cell proliferation, cytokine production (IL-2, IFN-gamma), and adhesion were measured.
  • Signaling pathways (PI3K/AKT, ERK/MAPK) and phosphatase activity (SHP-1, SHP-2) were analyzed.

Main Results:

  • PD-L2 negatively regulated T cell proliferation, IL-2, and IFN-gamma production via PD-1.
  • PD-1 was found to inhibit beta1 and beta2 integrin-mediated adhesion.
  • PD-L2 modulated PI3K/AKT and ERK/MAPK pathways, inhibiting AKT and ERK phosphorylation.
  • PD-L2 stimulation increased SHP-2 phosphatase activity and its association with PD-1.

Conclusions:

  • PD-L2 acts exclusively as a negative regulator of human T cell function through PD-1.
  • PD-1 plays a novel role in inhibiting integrin-mediated adhesion.
  • Catalytically active SHP-2 associated with PD-1 is implicated in PD-L2's modulation of T cell function.

More Related Videos

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes09:40

Co-immunoprecipitation Assay for Studying Functional Interactions Between Receptors and Enzymes

Published on: September 28, 2018

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.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Immunoglobulin-like Cell Adhesion Molecules01:31

Immunoglobulin-like Cell Adhesion Molecules

Immunoglobulin-like cell adhesion molecules or Ig-CAMs are a versatile group of cell surface glycoproteins belonging to the immunoglobulin protein superfamily. Ig-CAMs possess the characteristic immunoglobulin protein domains and other domains such as the fibronectin type III domain. The Ig domains are glycosylated to varying degrees in different Ig-CAMs.
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
Activation of Integrins01:15

Activation of Integrins

Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding events provide an effective stimulus.
Selectins01:25

Selectins

Cell adhesion is  an essential aspect of multicellularity. While stable cell interactions usually occur between cells of the same type, transient cell interactions occur between cells of different tissue types, such as between neutrophils and endothelial cells. Selectins are one class of cell adhesion molecules (CAMs) that bind carbohydrate ligands to form transient cell adhesion. They are rod-like proteins with a long extracellular part of variable length ending with the lectin domain, which...