B7-H3 is an orphan ligand in the B7 family. Its extended extracellular IgSF domain is unique within the family and is phylogenically found in primates only. B7-H3 is known as a co-stimulatory and co-inhibitory ligand, even though most studies indicate B7-H3 acts as an inhibitor for T cells functions. Consistent with the inhibitory notion, B7-H3 null mice exhibits an earlier onset of autoimmune disorders. P7105F contains all four extracellular IgV/C domains of B7-H3 and is fused with a mouse IgG2a Fc region.
Interacting protein(s): not known
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|Synonym:||CD276, 4Ig-B7-H3, B7H3, B7RP-2|
|MW (Calculated):||74,244 daltons|
|MW (SDS-PAGE):||77 Kd|
|Abs 0.1% (=1 mg/ml):||0.947|
B7-H3, a B-7-like molecule, was identified by searching database of NCBI with the sequences corresponding to the extracellular domain of all published B7 family members. While B7-h3 share similarities in its structural organization, it differs from other B7-like molecules in a few aspects. Though the “canonical” B7-like B7-H3 contains single IgV-IgC extracelluar region was initially identified, the unprecedented “dual” IgV-IgC-containing B7-H3 protein was subsequently identified. Interestingly, in contrast to the normal conservation of the B7 protein across species, the “dual” type B7-H3 is only found in primates but not in rodents.
In addition, to date, no receptor has been identified for B7-H3, even though it was shown that the counter receptor can be up-regulated on T and B cells, and the possibility of being CD28, CTLA-4, ICOS, or PD-1 has been ruled out. Furthermore, allograft can permanently survive in B7-H3-deficient mice with supplement of an immunosuppressant such as rapamycin or cyclosporine. This observation, in contrast to the observation that allograft was acutely rejected in the absence of CD28, underlies the possibility of targeting B7-H3 for transplantation rejection.
Lastly, B7-H3 was found not only on the APC, but also on the activated T cells, hence it has considered as a distinct functional category like LIGHT, where the inducible molecules are present on both APC and T cells and therefore the co-stimulation can occur in a T cell to T cell fashion.
Amino Acid Sequence
1. B7-H3: a costimulatory molecule for T cell activation and IFN-gamma production. Chapoval A.I., Ni J., Lau J.S., Wilcox R.A., Flies D.B., Liu D., Dong H., Sica G.L., Zhu G., Tamada K., Chen L. Nat. Immunol. 2:269-274 (2001)
2. B7-H3: another molecule marker for Mo-DCs? Zhang G.B., Dong Q.M., Xu Y., Yu G.H., Zhang X.G. Cell. Mol. Immunol. 2:307-311 (2005)
3. B7-H3 promotes acute and chronic allograft rejection. Wang L., Fraser C.C., Kikly K., Wells A.D., Han R., Coyle A.J., Chen L., Hancock W.W. Eur. J. Immunol. 35:428-438 (2005)
4. Triggering receptor expressed on myeloid cell-like transcript 2 (TLT-2) is a counter-receptor for B7-H3 and enhances T cell responses. Hashiguchi M., Kobori H., Ritprajak P., Kamimura Y., Kozono H., Azuma M. Proc. Natl. Acad. Sci. U.S.A. 105:10495-10500 (2008)