Structure and t cell inhibition properties of b7 family member, B7-H3

Vladimir Vigdorovich, Udupi A. Ramagopal, Eszter Lázár-Molnár, Eliezer Sylvestre, Jun Sik Lee, Kimberly A. Hofmeyer, Xingxing Zang, Stanley G. Nathenson, Steven C. Almo

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

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 Å 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.

Original languageEnglish (US)
Pages (from-to)707-717
Number of pages11
JournalStructure
Volume21
Issue number5
DOIs
StatePublished - May 7 2013

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T-Lymphocytes
Antigens
T-Cell Antigen Receptor
Immunoglobulins
Cell Proliferation
Organizations
Ligands
Neoplasms
Inhibition (Psychology)
Recognition (Psychology)

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

Cite this

Vigdorovich, V., Ramagopal, U. A., Lázár-Molnár, E., Sylvestre, E., Lee, J. S., Hofmeyer, K. A., ... Almo, S. C. (2013). Structure and t cell inhibition properties of b7 family member, B7-H3. Structure, 21(5), 707-717. https://doi.org/10.1016/j.str.2013.03.003

Structure and t cell inhibition properties of b7 family member, B7-H3. / Vigdorovich, Vladimir; Ramagopal, Udupi A.; Lázár-Molnár, Eszter; Sylvestre, Eliezer; Lee, Jun Sik; Hofmeyer, Kimberly A.; Zang, Xingxing; Nathenson, Stanley G.; Almo, Steven C.

In: Structure, Vol. 21, No. 5, 07.05.2013, p. 707-717.

Research output: Contribution to journalArticle

Vigdorovich, V, Ramagopal, UA, Lázár-Molnár, E, Sylvestre, E, Lee, JS, Hofmeyer, KA, Zang, X, Nathenson, SG & Almo, SC 2013, 'Structure and t cell inhibition properties of b7 family member, B7-H3', Structure, vol. 21, no. 5, pp. 707-717. https://doi.org/10.1016/j.str.2013.03.003
Vigdorovich V, Ramagopal UA, Lázár-Molnár E, Sylvestre E, Lee JS, Hofmeyer KA et al. Structure and t cell inhibition properties of b7 family member, B7-H3. Structure. 2013 May 7;21(5):707-717. https://doi.org/10.1016/j.str.2013.03.003
Vigdorovich, Vladimir ; Ramagopal, Udupi A. ; Lázár-Molnár, Eszter ; Sylvestre, Eliezer ; Lee, Jun Sik ; Hofmeyer, Kimberly A. ; Zang, Xingxing ; Nathenson, Stanley G. ; Almo, Steven C. / Structure and t cell inhibition properties of b7 family member, B7-H3. In: Structure. 2013 ; Vol. 21, No. 5. pp. 707-717.
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