Integrin alpha1beta1 (VLA-1) mediates adhesion of activated intraepithelial lymphocytes to collagen

Immunology. 1999 Aug;97(4):679-85. doi: 10.1046/j.1365-2567.1999.00812.x.


Intraepithelial lymphocytes (IELs) from human intestinal epithelium are memory CD8+ T cells that bind to epithelial cells through human mycosal lymphocyte (HML)-1 and to mesenchymal cells through very late activation antigen-4 (VLA-4). Their binding of extracellular matrix proteins and the mechanism involved were tested. Activated 51Cr-labelled lymphocytes were incubated in protein-coated microwells with various additives. After washing, the adherent cells were detected by radioactivity. The percentages of activated IELs that bound to collagen types I and IV were 20 and 31%, respectively; fewer bound to fibronectin or laminin. Compared to interleukin-2-activated peripheral blood CD8+ T lymphocytes, more IELs bound collagen IV and fewer bound fibronectin. IEL adhesion to collagen (but not fibronectin or laminin) was up-regulated by antibody ligation of CD2 or by protein kinase C stimulation by phorbol ester; staurosporine reduced binding, while herbimycin, phytohaemagglutinin and CD3 ligation had no effect. Antibody-blocking of integrin VLA-1 subunits alpha1 (CD49a) and beta1 (CD18) inhibited adhesion to collagen type I by 82+/-6% and to type IV by 94+/-1% (P<0.001), implicating VLA-1 as the main collagen receptor for IELs. Cell adhesion was dependent on extracellular divalent cations, a characteristic event of VLA-1 never before shown for IELs: manganese and magnesium ions supported binding in a dose-dependent manner; calcium ions inhibited their effectiveness. Therefore, IELs bind collagen through integrin alpha1beta1 after protein kinase C activation. Adhesion is modulated by divalent cations.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • CD8-Positive T-Lymphocytes / metabolism*
  • Cell Adhesion / immunology
  • Cell Culture Techniques
  • Collagen / metabolism*
  • Epithelial Cells / immunology*
  • Extracellular Matrix Proteins / metabolism
  • Humans
  • Integrin alpha1beta1
  • Integrins / metabolism*
  • Interleukin-2 / immunology
  • Intestinal Mucosa / immunology*
  • Lymphocyte Activation / immunology
  • Protein Kinase C / metabolism


  • Extracellular Matrix Proteins
  • Integrin alpha1beta1
  • Integrins
  • Interleukin-2
  • Collagen
  • Protein Kinase C