An unusual inhibitory receptor--the mast cell function-associated antigen (MAFA)

The mast cell function-associated antigen (MAFA) is a type II membranal glycoprotein that was first identified on the surface of rat mucosal-type mast cells of the RBL-2H3 line. A C-type lectin domain and an immunoreceptor tyrosine-based inhibitory motif (ITIM) are located in the extracellular and intracellular domains of MAFA, respectively. Human and mouse homologues of MAFA have been discovered recently. However, they are expressed also or only by NK and T-cells, where they most probably play different roles. MAFA clustering by its specific antibody mAb G63 has been previously shown to cause a dose-dependent inhibition of the secretory response of these cells to the FcepsilonRI stimulus. More recent results established that MAFA's inhibitory action involves at least two different enzymes: Following the tyrosyl-phosphorylation of MAFA ITIM by the PTK Lyn, two phosphatases SHIP and SHP2 are recruited to it at the plasma membrane where they propagate the inhibitory signals. The following is a brief report on this unusual inhibitory receptor and its functional activities.