NEGATIVE REGULATION OF FC-EPSILON-RI-MEDIATED DEGRANULATION BY CD81

Signaling through the high affinity receptor for immunoglobulin E (Fc epsilon RI) results in the coordinate activation of tyrosine kinases b efore calcium mobilization. Receptors capable of interfering with the signaling of antigen receptors, such as Fc epsilon RI, recruit tyrosin e and inositol phosphatases that results in diminished calcium mobiliz ation. Here, we show that antibodies recognizing CD81 inhibit Fc epsil on RI-mediated mast cell degranulation but, surprisingly, without affe cting aggregation-dependent tyrosine phosphorylation, calcium mobiliza tion, or leukotriene synthesis. Furthermore, CD81 antibodies also inhi bit mast cell degranulation in vivo as measured by reduced passive cut aneous anaphylaxis responses. These results reveal an unsuspected calc ium-independent pathway of antigen receptor regulation, which is acces sible to engagement by membrane proteins and on which novel therapeuti c approaches to allergic diseases could be based.