title: Comparative functional characterization of canine IgG subclasses.
abstract: To date, very little is known about the functional characteristics of the four published canine IgG subclasses. It is not clear how each subclass engages the immune system via complement-dependent cytotoxicity (CDC) or antibody-dependent cell-mediated cytotoxicity (ADCC), or how long each antibody may last in serum. Such information is critical for understanding canine immunology and for the discovery of canine therapeutic monoclonal antibodies. Through both in vitro and ex vivo experiments to evaluate canine Fc's for effector function, complement binding, FcRn binding, and ADCC, we are now able to categorize canine subclasses by function. The subclasses share functional properties with the four human IgG subclasses and are reported herein with their function-based human analog. Canine Fc fusions, canine chimeras, and caninized antibodies were characterized. Canine subclasses A and D appear effector-function negative while subclasses B and C bind canine Fc gamma receptors and are positive for ADCC. All canine subclasses bind the neonatal Fc receptor except subclass C. By understanding canine IgGs in this way, we can apply what is known of human immunology toward translational and veterinary medicine. Thus, this body of work lays the foundation for evaluating canine IgG subclasses for therapeutic antibody development and builds upon the fundamental scholarship of canine immunology.
authors.affiliation: Zoetis, Global Therapeutic Research, Veterinary Medicine Research and Development, 333 Portage Road, Kalamazoo, MI 49007, USA. Electronic address: Lisa.Bergeron@zoetis.com.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Bergeron
authors.affiliation: Zoetis, Global Therapeutic Research, Veterinary Medicine Research and Development, 333 Portage Road, Kalamazoo, MI 49007, USA.
authors.forename: Erin E
authors.initials: EE
authors.lastname: McCandless
authors.affiliation: Zoetis, Global Therapeutic Research, Veterinary Medicine Research and Development, 333 Portage Road, Kalamazoo, MI 49007, USA.
authors.forename: Steve
authors.initials: S
authors.lastname: Dunham
authors.affiliation: Zoetis, Global Therapeutic Research, Veterinary Medicine Research and Development, 333 Portage Road, Kalamazoo, MI 49007, USA.
authors.forename: Bill
authors.initials: B
authors.lastname: Dunkle
authors.affiliation: Zoetis, Global Therapeutic Research, Veterinary Medicine Research and Development, 333 Portage Road, Kalamazoo, MI 49007, USA.
authors.forename: Yaqi
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Zoetis, Global Therapeutic Research, Veterinary Medicine Research and Development, 333 Portage Road, Kalamazoo, MI 49007, USA.
authors.forename: John
authors.initials: J
authors.lastname: Shelly
authors.affiliation: Zoetis, Global Therapeutic Research, Veterinary Medicine Research and Development, 333 Portage Road, Kalamazoo, MI 49007, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Lightle
authors.affiliation: Zoetis, Global Therapeutic Research, Veterinary Medicine Research and Development, 333 Portage Road, Kalamazoo, MI 49007, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gonzales
authors.affiliation: Zoetis, Global Therapeutic Research, Veterinary Medicine Research and Development, 333 Portage Road, Kalamazoo, MI 49007, USA.
authors.forename: Graeme
authors.initials: G
authors.lastname: Bainbridge
mesh_terms: D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D003001:Cloning, Molecular; D003429:Cross Reactions / Q000276:immunology; D004285:Dogs / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D051379:Mice; D012313:RNA / Q000737:chemistry / Q000235:genetics; D019105:Random Amplified Polymorphic DNA Technique / Q000662:veterinary; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D007074:Immunoglobulin G; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins; D012313:RNA
keywords: ADCC; CDC; CDR; Canine; Effector functions; Fc receptor; IgG subclass; Immunoglobulin; antibody-dependent cell-mediated cytotoxicity; cell-mediated cytotoxicity; complementarity determining region