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

Research output: Contribution to journalArticlepeer-review

109 Scopus citations

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

ASJC Scopus subject areas

  • General

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