RT Journal Article
SR Electronic
T1 Integrin alpha 4 / beta 1 (CD49d/CD29) is a component of the murine IgG3 receptor
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 207274
DO 10.1101/207274
A1 Carolyn Saylor Hawk
A1 Carolina Coelho
A1 Diane Sthefany Lima de Oliveira
A1 Verenice Paredes
A1 Patrícia Albuquerque
A1 Anamélia Lorenzetti Bocca
A1 Ananésia Correa dos Santos
A1 Victoria Rusakova
A1 Heather Holemon
A1 Maria Sueli Soares Felipe
A1 Hideo Yagita
A1 André Moraes Nicola
A1 Arturo Casadevall
YR 2017
UL http://biorxiv.org/content/early/2017/10/21/207274.abstract
AB Antibodies exert several of their effector functions by binding to cell surface receptors. For murine IgG3 (mIgG3) the identity of its receptors (and the very existence of a receptor) is still under debate, as not all mIgG3 functions can be explained by interaction with Fcγ-receptor I (FcγRI). This implies the existence of an alternate receptor, whose identity we sought to pinpoint. We found that blockage of the alpha4/beta1 integrin (Itga4/Itgb1) selectively hampered binding of mIgG3 to macrophages and mIgG3-mediated phagocytosis. Manganese, an integrin activator, increased mIgG3 binding to macrophages. Blockage of FcγRI or Itgb1 inhibited binding of different mIgG3 antibodies to variable extents. Our results indicate an integrin component in the mIgG3 receptor. Given the more ancient origin of integrins in comparison with FcγR, this observation could have far ranging implications for our understanding of the evolution of antibody-mediated immunity, as well as in immunity to microorganisms, pathogenesis of autoimmune diseases and antibody engineering.