Tenascin-C inhibits beta 1 integrin-dependent T lymphocyte adhesion to fibronectin through the binding of its fnlll 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 prot eins is mainly regulated at the adhesion receptor level, but it is conceiva ble that the composition df the matrix itself may affect T lymphocyte adhes ion to individual proteins. We have addressed the latter paint 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 lymphocyte s and MOLT-4 lymphoma cells to fibronectin. We demonstrate that a TN-C frag ment consisting of fibronectin type III repeats 1-5 (TNfnIII 1-5) but not T NfnIII A-D and TNfnIII 6-8 inhibited alpha 5 beta 1 and alpha 4 beta 1 inte grin-mediated T lymphocyte and MOLT-4 adhesion to fibronectin. At concentra tions that did not inhibit adhesion, TNfnIII 1-5 still prevented MOLT-4 cel ls from spreading on fibronectin. Preincubation and co-immobilization of TN fnIII 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 inhibiti on of T lymphocyte adhesion to fibronectin caused by TN-C, and indicate tha t this effect involves the binding of TN-C repeats TNfnIII 1-5 to fibronect in.