Integrin-associated protein (CD47) is a comitogenic molecule on CD3-activated human T cells.
IAP is a glycoprotein functionally and physically associated with some integrins, i.e., the leukocyte response integrin and the beta3 integrin chain on placenta, platelets, and polymorphonuclear cells. IAP may act as a transducer element in activation mediated via these integrins. Since IAP is present at high density on peripheral T lymphocytes we have investigated its involvement in T cell activation. We tested three mAbs against IAP, namely B6H12, BRIC126, and 2D3, which recognize two distinct epitopes. IAP cross-linking with B6H12 or BRIC126, but not 2D3, transduces costimulatory signals within highly purified CD3-activated T lymphocytes, i.e., enhancement of proliferation, CD25 expression, and IL-2 secretion, while no effect was observed upon CD2 stimulation. However, we could not observe any functional association between IAP and integrins on peripheral T cells. In an attempt to explore further the activation signal delivered by IAP, we show here that IAP cross-linking with the comitogenic B6H12 mAb induces the phosphorylation on tyrosine of several proteins, one of which is identified as p56(lck) protein tyrosine kinase. Moreover, we observed that IAP is associated with p56(lck) on PMA-activated, but not on resting, T cells. These data suggest that on T cells, IAP may be involved directly via a specific ligand in cell-matrix or cell-cell interactions. Such interactions could trigger protein tyrosine phosphorylation pathways, which play an important role in both maturation and activation of T cells.
Ticchioni
M
M
INSERM Unit 343, Immunology Laboratory, Archet Hospital, Nice, France.
Deckert
M
M
Mary
F
F
Bernard
G
G
Brown
E J
EJ
Bernard
A
A
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology*; D017252:CD3 Complex / Q000276:immunology* / Q000494:pharmacology*; D051928:CD47 Antigen; D002352:Carrier Proteins / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology*; D004357:Drug Synergism; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000187:drug effects*; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D008934:Mitogens / Q000276:immunology* / Q000494:pharmacology*; D011485:Protein Binding / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019061:src-Family Kinases / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D017252:CD3 Complex; D051928:CD47 Antigen; C497894:CD47 protein, human; D002352:Carrier Proteins; D008934:Mitogens; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D019061:src-Family Kinases; D013755:Tetradecanoylphorbol Acetate