Cell spreading distinguishes the mechanism of augmentation of T cell activation by integrin-associated protein/CD47 and CD28

Int Immunol. 1999 May;11(5):707-18. doi: 10.1093/intimm/11.5.707.


Integrin-associated protein (IAP/CD47) is a 50 kDa transmembrane protein initially defined as a regulator of beta3 integrin-mediated functions in neutrophils. IAP also can synergize with the TCR in T cell activation independent of beta3 integrins. To analyze the mechanism for IAP synergy with TCR, we expressed in Jurkat cells a chimeric molecule, consisting of the CD16 extracellular domain, the CD7 transmembrane domain and the TCR zeta chain cytoplasmic tail (CD16-7-zeta), which on its own is unable to induce IL-2 production. Ligation of IAP acted in synergy with TCR to induce IL-2 transcription and synthesis, but failed to synergize with the signal generated by CD16-7-zeta, while CD28 was a potent co-stimulator with both TCR and CD16-7-zeta. The failure of IAP to activate Jurkat together with CD16-7-zeta correlated with a lack of c-Jun N-terminal kinase, but not extracellular-signal-regulated kinase activation. Jurkat adhesion to anti-IAP, but not anti-CD28, induced cell spreading and the same domains of IAP required for augmentation of T cell activation were required to induce cell spreading. IAP synergy with TCR signaling likely results from its ability to stimulate adhesion to a ligand-expressing surface or antigen-presenting cell (APC), rather than from initiation of a novel signaling cascade. We conclude that a major role for ligation of IAP in T cell activation is to enhance the efficiency of TCR signaling by causing T cells to spread on an APC or surface.

Publication types

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

MeSH terms

  • Antigens, CD / physiology*
  • CD28 Antigens / physiology*
  • CD3 Complex / physiology
  • CD47 Antigen
  • Carrier Proteins / physiology*
  • Humans
  • Interleukin-2 / biosynthesis
  • JNK Mitogen-Activated Protein Kinases*
  • Jurkat Cells
  • Lymphocyte Activation*
  • MAP Kinase Kinase 4
  • Membrane Proteins / physiology
  • Mitogen-Activated Protein Kinase Kinases*
  • Mitogen-Activated Protein Kinases / physiology
  • Protein Kinases / physiology
  • Receptors, Antigen, T-Cell / physiology
  • Receptors, IgG / physiology
  • T-Lymphocytes / immunology*


  • Antigens, CD
  • CD28 Antigens
  • CD3 Complex
  • CD47 Antigen
  • CD47 protein, human
  • Carrier Proteins
  • Interleukin-2
  • Membrane Proteins
  • Receptors, Antigen, T-Cell
  • Receptors, IgG
  • antigen T cell receptor, zeta chain
  • Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4
  • Mitogen-Activated Protein Kinase Kinases