Human B7-H3 was originally identified as a 316 amino acid (aa) type I membrane precursor protein with a putative 28 aa signal peptide, a 217 aa extracellular region containing one V-like and one C-like Ig domain, a transmembrane region, and a 45 aa cytoplasmic domain. Subsequently, a second dominantly expressed form of human B7-H3, containing a splice variation that duplicates the V-like and C-like Ig domains, was found. The 534 aa splice variant of B7-H3 has been referred to as B7-H3b, 4Ig-B7-H3, and B7-H3VCVC. RTPCR transcripts for both B7-H3 and 4Ig-B7-H3 have been found in all tissues except peripheral blood leukocytes. Southern blot analysis indicates that the 4Ig-B7-H3 isoform of B7-H3 is the predominate isoform expressed in human tissues.

In mouse, only a single form of B7-H3 containing one V-like and one C-like Ig domain was detected. Mouse and human B7-H3 share 87% aa sequence identity. B7-H3 has been shown to be expressed at very high levels in immature dendritic cells, at moderate levels on mature dendritic cells, LPS stimulated immature dendritic cells and LPS stimulated monocytes, and at low levels on resting monocytes. B7-H3 binds to activated T cells via an as yet unidentified receptor.