A functional monoclonal antibody recognizing the human alpha 1-integrin I-domain.
Alpha 1 beta 1 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 alpha 1 integrin belongs to a subset of I-domain containing integrins that includes alpha M, alpha L, alpha X and alpha 2. In this study we describe an anti-alpha 1 mAb (FB12) that recognizes an epitope located in the human alpha 1 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 alpha 1 I-domain itself has an important role in receptor-ligand binding. In particular, we show that alpha 1 integrin-dependent lymphocyte adhesion to fibronectin is I-domain mediated, at variance with the RGD-dependent adhesion which seems to be mediated by the beta 1 rather than the alpha 1 integrin chain. Lastly, the overexpression of the alpha 1-integrin by stromal cells and blood vessels of solid tumors may suggest a role for this integrin in tumor biology.
Fabbri
M
M
Human Immunology Unit, Dibit Milan, Italy.
Castellani
P
P
Gotwals
P J
PJ
Kotelianski
V
V
Zardi
L
L
Zocchi
M R
MR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D003094:Collagen / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006367:HeLa Cells / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D039423:Integrin alpha1; D016023:Integrins / Q000235:genetics / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D007797:Laminin / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000276:immunology; D016133:Polymerase Chain Reaction; D051381:Rats
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D005353:Fibronectins; D039423:Integrin alpha1; D016023:Integrins; D007797:Laminin; D003094:Collagen