Tenascin‐C inhibits β1 integrin‐dependent T lymphocyte adhesion to fibronectin through the binding of its fnIII 1 – 5 repeats to fibronectin

• Published in: European journal of immunology Vol. 29; no. 5; pp. 1435 - 1447
• Main Authors: Hauzenberger, Dan, Olivier, Philippe, Gundersen, Doris, Rüegg, Curzio
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag GmbH 01.05.1999
• Subjects: Cell adhesion; Integrin; Tenascin‐C
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/(SICI)1521-4141(199905)29:05<1435::AID-IMMU1435>3.0.CO;2-N

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 TNC fragment consisting of fibronectin type III repeats 1 – 5 (TNfnIII 1 – 5) but not TNfnIII A – D and TNfnIII 6 – 8 inhibited α5β1 and α4β1 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.