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Structure of Murine CTLA-4 and Its Role in Modulating T Cell Responsiveness

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Science  27 Oct 2000:
Vol. 290, Issue 5492, pp. 816-819
DOI: 10.1126/science.290.5492.816

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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.

  • * To whom correspondence should be addressed. E-mail: almo{at}aecom.yu.edu or nathenso{at}aecom.yu.edu

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