Physical association and functional interaction between beta1 integrin and CD98 on human T lymphocytes

Yuko J Miyamoto1, Jason S Mitchell, Bradley W McIntyre

  • 1Department of Immunology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 180, Houston, TX 77030, USA.

Molecular Immunology
|January 18, 2003
PubMed

Insights

CD98 protein physically associates with alpha4beta1 integrin on human T lymphocytes. This association is crucial for CD98-mediated homotypic T cell aggregation and may play a role in lymphocyte proliferation and adhesion.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • CD98 is a cell surface protein with roles in T cell activation, amino acid transport, and integrin function.
  • Integrins are vital for T cell aggregation, adhesion, and coactivation.
  • Previous studies suggested a functional link between CD98 and beta1 integrin signaling in T cells.

Purpose of the Study:

  • To investigate the physical association between CD98 and beta1 integrin in human T lymphocytes.
  • To elucidate the role of this physical association in CD98-mediated T cell functions.

Main Methods:

  • Induction of homotypic aggregation via CD98 stimulation.
  • Inhibition studies using anti-beta1 integrin monoclonal antibodies (mAbs).
  • Competitive binding assays and fluorescence colocalization.
  • Differential extraction and immunoprecipitation techniques.

Main Results:

  • CD98 stimulation induced homotypic T cell aggregation, which was inhibited by anti-beta1 integrin mAb.
  • Competitive binding and colocalization assays indicated a physical association between CD98 and beta1 integrin.
  • Immunoprecipitation confirmed the specific association of alpha4beta1 integrin with CD98 on human T lymphocytes.

Conclusions:

  • CD98 physically associates with alpha4beta1 integrin on human T lymphocytes.
  • This physical interaction is involved in CD98-mediated homotypic T cell aggregation.
  • The findings suggest integrins are integral to CD98-dependent lymphocyte proliferation and adhesion.

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...
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...
Integrins01:10

Integrins

Animal and protozoan cells do not have cell walls to help maintain shape and provide structural stability. Instead, these eukaryotic cells secrete a sticky mass of carbohydrates and proteins into the spaces between adjacent cells. This network of proteins and molecules is called an extracellular matrix or ECM.
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
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.
Cell Adhesion Molecules - Types and Functions01:20

Cell Adhesion Molecules - Types and Functions

Cell adhesion molecules (CAMs) are pivotal to multicellularity and the coordinated functioning of tissues and organ systems. They enable physical interactions between cells and provide mechanical strength to tissues. They also function as receptors for signal transmission across the plasma membrane. The CAMs are broadly classified into four families - integrins, cadherins, selectins, and immunoglobulin-like CAMs (IgCAMs).
CAM Families
The Integrin family of proteins is primarily  involved in a...
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...