Identification of CD16-2, a novel mouse receptor homologous to CD16/FcγRIII

Abstract.

It is believed that mouse FcγRIII arose by an evolutionarily recent recombination, which brought together the extracellular domains from FcγRII with the transmembrane/cytoplasmic region from the ancestor FcγRIII. Here, we report identification of a mouse gene encoding a transmembrane receptor that may be regarded as the true ortholog of nonrodent CD16/FcγRIII. Designated CD16-2, the novel protein is highly similar to human FcγRIIIA in the signal peptide (60% identical residues), and in the extracellular domains (65%). Although the similarity between the two proteins is less conspicuous in the transmembrane/cytoplasmic region (54%), it is higher than between human FcγRIIIA and mouse FcγRIII (44%). However, the conserved transmembrane motif LFAVDTGL shared by rodent and human FcγRIII and FcεRI has two replacements in CD16-2. The CD16-2 gene is tightly linked to the FcγRIII and FcγRII genes and consists of five exons. Northern blot analysis revealed that CD16-2 is expressed in peripheral blood leukocytes, as well as in spleen, thymus, colon and intestine. RT-PCR showed prominent expression in macrophage cell line J774. Based on sequence comparisons, it is suggested that the modern repertoire of the mammalian low affinity Fc receptors has resulted from repetitive duplications and/or recombinations of three ancestral genes.