Costimulatory B7 molecules (e.g., B7-1, or CD80; 112203) signal through CD28 (186760) family molecules, such as CD28, CTLA4 (123890), and ICOS (604558). By searching sequence databases with the extracellular regions of B7 family members, Chapoval et al. (2001) identified a cDNA encoding CD276, which they called B7H3, in a dendritic cell (DC) cDNA library. Sequence analysis predicted that the 316-amino acid type I transmembrane protein contains an N-terminal signal peptide; extracellular V- and C-like Ig domains with 4 conserved cysteine residues; a transmembrane region; and a 45-amino acid cytoplasmic tail. The extracellular receptor-binding domain of B7H3 shares 27% and 25% identity with those of B7H1 (605402) and B7H2 (605717), respectively. Northern blot analysis detected highest expression of a 4.1-kb transcript in heart, liver, placenta, prostate, testis, uterus, pancreas, small intestine, colon, and lymphoid organs, with lower expression in brain, skeletal muscle, kidney, and lung, and no expression in peripheral blood leukocytes. B7H3 expression was detected in most tumor cell lines tested. Sun et al. (2002) identified a mouse homolog of B7H3. By probing an EST database using mouse B7h3, they identified a human B7H3 variant, which they termed B7H3b, that has a different N-terminal sequence. RT-PCR analysis detected wide expression of both B7H3 isoforms. B7H3b was the major isoform in all tissues examined except brain and placenta. Using monoclonal antibodies reacting with monocyte-derived DCs, retroviral expression cloning, and flow cytometric analysis, Steinberger et al. (2004) obtained a cDNA identical to the B7H3 cDNA reported by Chapoval et al. (2001) at its 5-prime end. However, full-length DNA sequence analysis indicated that B7H3 encodes a 534-amino acid protein with a short leader sequence and 4, rather than 2, Ig-like domains, followed by a transmembrane domain and a short cytoplasmic tail. RT-PCR and EST database analyses showed that only the 1.3-kb transcript corresponding to the larger molecule was expressed in various tissues and cell lines. Western blot analysis revealed strong expression of a 110-kD protein corresponding to the larger molecule in both mature and immature DCs.