Modulates T-cell-mediated immune responses and the development of acute and chronic transplant rejection. Plays a positive regulatory role in bone formation and has a dual role in the bone-immune interface. Induces antitumor immunity as it activates both acquired and innate immunity leading to natural killer cell and CD8 T-cell dependent killing of tumor cells. Interacts with TREML2 and this interaction enhances T-cell activation. Ubiquitous. Highly expressed in developing bones during embryogenesis and expression increases as osteoblast precursor cells differentiate into mature osteoblasts. Up-regulated in cells mediating rejection of mouse transplant. Mice display a lower bone mineral density in cortical bones with femurs more susceptible to bone fracture, but do not exhibit any important skeletal abnormalities. Calvarial cells reveal normal number of osteoblast precursor cells with adequate proliferative capacity, but have impaired osteogenic differentiation. Furthermore, following cardiac transplantation, they display permanent survival under rapamycin regimen and cardiac transplants also show markedly decreased production of key cytokine and chemokine. The incidence of chronic transplant rejection is also inhibited. Mice also develop more severe airway inflammation and experimental autoimmune encephalomyelitis earlier than wild-type littermates as well as accumulate higher concentrations of autoantibodies to DNA. Gene transfer of B7-H3 leads to complete regression of 50 per cent tumors, or significantly slows tumor growth. In primates, B7-H3 locus underwent genomic duplication leading to tandemly repeated immunoglobulin-like V and C domains (VC domains). The dominantly expressed human B7-H3 isoform contains tandemly duplicated VC domains. In contrast, mouse B7-H3 transcript contains only one single VC domain form due to an exon structure corresponding to V domain-(pseudoexon C)-(pseudoexon V)-C domain. This duplication appearing in primates is suggested to be very recent supporting a model of multiple independent emergence of tandem VC repeats within human and monkey species. Belongs to the immunoglobulin superfamily. BTN/MOG family.