Tenascin-C inhibits beta1 integrin-dependent T lymphocyte adhesion to fibronectin through the binding of its fnIII 1-5 repeats to fibronectin.
The extracellular matrix consists of different proteins interacting to form a meshwork-like structure. T lymphocyte adhesion to individual matrix proteins is mainly regulated at the adhesion receptor level, but it is conceivable that the composition of the matrix itself may affect T lymphocyte adhesion to individual proteins. We have addressed the latter point by studying the effect of the matrix protein tenascin-C (TN-C) on T lymphocyte adhesion to fibronectin. Here we report that TN-C inhibits adhesion of T lymphocytes and MOLT-4 lymphoma cells to fibronectin. We demonstrate that a TN-C fragment consisting of fibronectin type III repeats 1-5 (TNfnIII 1-5) but not TNfnIII A-D and TNfnIII 6-8 inhibited alpha5beta1 and alpha4beta1 integrin-mediated T lymphocyte and MOLT-4 adhesion to fibronectin. At concentrations that did not inhibit adhesion, TNfnIII 1-5 still prevented MOLT-4 cells from spreading on fibronectin. Preincubation and co-immobilization of TNfnIII 1-5 with fibronectin was more effective in inhibiting MOLT-4 adhesion to fibronectin than soluble TNfnIII 1-5 present during the adhesion test. Using an enzyme-linked immunosorbent assay we could demonstrate binding of TNfnIII 1-5 to fibronectin and fibronectin fragments. Taken together, these data demonstrate that the TNfnIII 1-5 domain is implicated in the inhibition of T lymphocyte adhesion to fibronectin caused by TN-C, and indicate that this effect involves the binding of TN-C repeats TNfnIII 1-5 to fibronectin.
Hauzenberger
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D
Laboratory of the Centre Pluridisciplinaire d'Oncologie at the Swiss Institute for Experimental Cancer Research, Epalinges.
Olivier
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P
Gundersen
D
D
Rüegg
C
C
D001665:Binding Sites; D002448:Cell Adhesion; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000378:metabolism*; D017469:Receptors, Fibronectin / Q000378:metabolism*; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism*; D012995:Solubility; D013601:T-Lymphocytes / Q000378:metabolism* / Q000502:physiology; D019063:Tenascin / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D005353:Fibronectins; D039041:Integrin alpha4beta1; D016023:Integrins; D017469:Receptors, Fibronectin; D016201:Receptors, Lymphocyte Homing; D019063:Tenascin