A functional monoclonal antibody recognizing the human alpha1-integrin I-domain

α1β1 heterodimer is a member of the integrin receptor superfamily that has been described to be involved in cell-matrix binding through its interaction with collagens, fibronectin and laminin. The α1 integrin belongs to a subset of I-domain containing integrins that includes α(M), α(L), α(X) and α2. In this study we describe an anti-α1 mAb (FB12) that recognizes an epitope located in the human α1 I-domain, since the mAb can bind to human, but not to rat, recombinant I-domain GST fusion protein. FB12 mAb efficiently and specifically inhibits the binding of activated human lymphocytes to laminin, collagen and fibronectin. These data support the notion that the α1 I-domain itself has an important role in receptor-ligand binding. In particular, we show that α1 integrin-dependent lymphocyte adhesion to fibronectin is I-domain mediated, at variance with the RGD-dependent adhesion which seems to be mediated by the β1 rather than the α1 integrin chain. Lastly, the overexpression of the α1-integrin by stromal cells and blood vessels of solid tumors may suggest a role for this integrin in tumor biology.