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

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

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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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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