| Structural highlights
Function
[CD276_MOUSE] 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.[1] [2] [3] [4] [5]
Publication Abstract from PubMed
T cell activity is controlled by a combination of antigen-dependent signaling through the T cell receptor and a set of auxiliary signals delivered through antigen-independent interactions, including the recognition of the B7 family of ligands. B7-H3 is a recently identified B7 family member that is strongly overexpressed in a range of cancers and correlates with poor prognosis. We report the crystal structure of murine B7-H3 at a 3 A resolution, which provides a model for the organization of the IgV and IgC domains within the ectodomain. We demonstrate that B7-H3 inhibits T cell proliferation and show that the FG loop of the IgV domain plays a critical role in this function. B7-H3 crystallized as an unusual dimer arising from the exchange of the G strands in the IgV domains of partner molecules. This arrangement, in combination with previous reports, highlights the dynamic nature and plasticity of the immunoglobulin fold.
Structure and T cell inhibition properties of B7 family member, B7-H3.,Vigdorovich V, Ramagopal UA, Lazar-Molnar E, Sylvestre E, Lee JS, Hofmeyer KA, Zang X, Nathenson SG, Almo SC Structure. 2013 May 7;21(5):707-17. doi: 10.1016/j.str.2013.03.003. Epub 2013 Apr, 11. PMID:23583036[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Sun M, Richards S, Prasad DV, Mai XM, Rudensky A, Dong C. Characterization of mouse and human B7-H3 genes. J Immunol. 2002 Jun 15;168(12):6294-7. PMID:12055244
- ↑ Suh WK, Gajewska BU, Okada H, Gronski MA, Bertram EM, Dawicki W, Duncan GS, Bukczynski J, Plyte S, Elia A, Wakeham A, Itie A, Chung S, Da Costa J, Arya S, Horan T, Campbell P, Gaida K, Ohashi PS, Watts TH, Yoshinaga SK, Bray MR, Jordana M, Mak TW. The B7 family member B7-H3 preferentially down-regulates T helper type 1-mediated immune responses. Nat Immunol. 2003 Sep;4(9):899-906. Epub 2003 Aug 17. PMID:12925852 doi:http://dx.doi.org/10.1038/ni967
- ↑ Sun X, Vale M, Leung E, Kanwar JR, Gupta R, Krissansen GW. Mouse B7-H3 induces antitumor immunity. Gene Ther. 2003 Sep;10(20):1728-34. PMID:12939639 doi:http://dx.doi.org/10.1038/sj.gt.3302070
- ↑ Prasad DV, Nguyen T, Li Z, Yang Y, Duong J, Wang Y, Dong C. Murine B7-H3 is a negative regulator of T cells. J Immunol. 2004 Aug 15;173(4):2500-6. PMID:15294965
- ↑ Wang L, Fraser CC, Kikly K, Wells AD, Han R, Coyle AJ, Chen L, Hancock WW. B7-H3 promotes acute and chronic allograft rejection. Eur J Immunol. 2005 Feb;35(2):428-38. PMID:15682454 doi:http://dx.doi.org/10.1002/eji.200425518
- ↑ Vigdorovich V, Ramagopal UA, Lazar-Molnar E, Sylvestre E, Lee JS, Hofmeyer KA, Zang X, Nathenson SG, Almo SC. Structure and T cell inhibition properties of B7 family member, B7-H3. Structure. 2013 May 7;21(5):707-17. doi: 10.1016/j.str.2013.03.003. Epub 2013 Apr, 11. PMID:23583036 doi:http://dx.doi.org/10.1016/j.str.2013.03.003
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