Molecular cloning and characterization of guinea pig Fc gamma RIII: expression but not function is independent of the gamma chain of Fc epsilon RI.

Abstract

We have isolated two cDNA clones encoding the guinea pig receptor for the Fc portion of IgG2 (Fc gamma 2R) from a guinea pig peritoneal macrophage cDNA library. Analysis of the predicted amino acid sequence of the one cDNA clone indicated that the guinea pig Fc gamma 2R is a type I transmembrane protein and has approximately 72% DNA sequence homology and approximately 57% protein sequence homology with the human Fc gamma RIII. Therefore, we propose that the guinea pig Fc gamma 2R is referred to as guinea pig Fc gamma RIII. The most important finding in this report is that the obtained cDNA directed the cell surface expression of the Fc gamma 2R on COS-7 cells without association with the gamma chain of the high-affinity IgE receptor (Fc epsilon RI gamma) which is required for human and mouse Fc gamma RIII to be expressed on the cell surface. Furthermore, we demonstrated that the endocytosis activity of Fc gamma RIII is dependent upon the association with Fc epsilon RI gamma, suggesting that Fc epsilon RI gamma is involved in the functions of guinea pig Fc gamma RIII. The other clone was found to lack the sequence encoding transmembrane and cytoplasmic domains, suggesting the presence of a soluble form of guinea pig Fc gamma RIII. Northern blot analysis and RT-PCR showed that a transmembrane form of guinea pig Fc gamma RIII was expressed in peritoneal macrophages, but not in neutrophils in spite of the fact that they express Fc gamma 2R, indicating that the Fc gamma 2R on neutrophils is a product of a distinct gene.