Porcine Fc gammaRIII isoforms are generated by alternative splicing.
The Fc gammaRIII plays an essential role in antibody-mediating effector functions of immune cells. Here, we report that transcripts encoding porcine Fc gammaRIII isoforms are generated by alternative splicing. Fc gammaRIII a.1 is expressed on the cell surface while Fc gammaRIII a.2 is secreted from the transfected cells due to a partial deletion of the transmembrane domain. Interestingly, a putative soluble Fc gammaRIII (sCD16) is detected in circulating plasma. Both Fc gammaRIII a.2 and sCD16 exhibit a similar molecular mass (approximately 35 kDa) and contain the extracellular D2 domains that are structurally intact. Despite the D2 domain deletion, Fc gammaRIII a.3 associates with Fc gammaRIII a.1. Hence, these results suggest one possibility that three Fc gammaRIII isoforms differentially modulate Fc gammaRIII-mediated immune responses in the porcine system. Furthermore, we demonstrate that a cytolytic triggering G7 monoclonal antibody recognizes the D2 domain that is responsible for interacting with the immune complexes and subsequent activations of porcine innate immune cells. This result suggests that the D2 domain is a target region to develop therapeutic antibodies that regulate the FcR-mediated immune responses.
Jie
Hyun-Bae
HB
Asthma Research, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 49229-3039, USA.
Yim
Daesong
D
Kim
Yoon B
YB
D017398:Alternative Splicing; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009000:Monocytes / Q000276:immunology; D020033:Protein Isoforms / Q000097:blood / Q000235:genetics / Q000276:immunology; D017434:Protein Structure, Tertiary; D017452:Receptors, IgG / Q000097:blood / Q000235:genetics / Q000276:immunology*; D013552:Swine
D000911:Antibodies, Monoclonal; D020033:Protein Isoforms; D017452:Receptors, IgG