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The HOD antigen is a transgenic triple-fusion protein expressed selectively on the surface of red blood cells (RBCs) in specialized mouse models. It consists of hen egg lysozyme (HEL), a segment of chicken ovalbumin (OVA), and the human Duffy blood group antigen (Fyb) [1, 2]. Developed as a standardized research tool in transfusion medicine, the HOD model allows scientists to precisely track immune responses to RBC antigens using existing transgenic T-cell and B-cell tools, such as OT-II mice, because HEL and OVA are highly characterized immunogens [3, 7]. In preclinical research, the HOD antigen is primarily used to investigate RBC alloimmunization, a major clinical challenge for patients requiring chronic blood transfusions, such as those with sickle cell disease or thalassemia [2, 4]. It serves as a target for studying delayed hemolytic transfusion reactions (DHTRs) and antigen modulation, where the binding of antibodies causes the antigen to be removed from the RBC surface without destroying the cell itself [5, 9]. While it is an artificial construct and not a therapeutic target in humans, it is critical for testing novel immunomodulatory therapies designed to prevent or treat life-threatening immune responses to transfused blood [7, 12].
The HOD antigen serves as an immunogenic target on the surface of transgenic red blood cells in murine models, allowing researchers to study the mechanisms of alloantibody formation, immune-mediated cell clearance, and the efficacy of immunosuppressive agents in preventing transfusion reactions [1, 5].
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