Structure of murine CTLA-4 and its role in modulating T cell responsiveness

D. A. Ostrov, W. Shi, J. C D Schwartz, Steven C. Almo, S. G. Nathenson

Research output: Contribution to journalArticle

104 Citations (Scopus)

Abstract

The effective regulation of T cell responses is dependent on opposing signals transmitted through two related cell-surface receptors, CD28 and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4). Dimerization of CTLA-4 is required for the formation of high-avidity complexes with B7 ligands and for transmission of signals that attenuate T cell activation. We determined the crystal structure of the extracellular portion of CTLA-4 to 2.0 angstrom resolution. CTLA-4 belongs to the immunoglobulin superfamily and displays a strand topology similar to Vα domains, with an unusual mode of dimerization that places the B7 binding sites distal to the dimerization interface. This organization allows each CTLA-4 dimer to bind two bivalent B7 molecules and suggests that a periodic arrangement of these components within the immunological synapse may contribute to the regulation of T cell responsiveness.

Original languageEnglish (US)
Pages (from-to)816-820
Number of pages5
JournalScience
Volume290
Issue number5492
DOIs
StatePublished - Oct 27 2000

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CTLA-4 Antigen
T-Lymphocytes
Dimerization
Immunological Synapses
B7 Antigens
Cell Surface Receptors
Immunoglobulins
Binding Sites
Ligands

ASJC Scopus subject areas

  • General

Cite this

Ostrov, D. A., Shi, W., Schwartz, J. C. D., Almo, S. C., & Nathenson, S. G. (2000). Structure of murine CTLA-4 and its role in modulating T cell responsiveness. Science, 290(5492), 816-820. https://doi.org/10.1126/science.290.5492.816

Structure of murine CTLA-4 and its role in modulating T cell responsiveness. / Ostrov, D. A.; Shi, W.; Schwartz, J. C D; Almo, Steven C.; Nathenson, S. G.

In: Science, Vol. 290, No. 5492, 27.10.2000, p. 816-820.

Research output: Contribution to journalArticle

Ostrov, DA, Shi, W, Schwartz, JCD, Almo, SC & Nathenson, SG 2000, 'Structure of murine CTLA-4 and its role in modulating T cell responsiveness', Science, vol. 290, no. 5492, pp. 816-820. https://doi.org/10.1126/science.290.5492.816
Ostrov, D. A. ; Shi, W. ; Schwartz, J. C D ; Almo, Steven C. ; Nathenson, S. G. / Structure of murine CTLA-4 and its role in modulating T cell responsiveness. In: Science. 2000 ; Vol. 290, No. 5492. pp. 816-820.
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