Binding Stoichiometry of the Cytotoxic T Lymphocyte-associated Molecule-4 (CTLA-4)

CD28 and CTLA-4 are homologous T cell receptors of the immunoglobulin (Ig) superfamily, which bind B7 molecules (CD80 and CD86) on antigen-presenting cells and transmit important costimulatory signals during T cell activation. Here we have investigated the subunit structure of CTLA-4 and the stoichi...

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Bibliographic Details
Published in:The Journal of biological chemistry 1995-06, Vol.270 (25), p.15417-15424
Main Authors: Linsley, Peter S., Nadler, Steven G., Bajorath, Jürgen, Peach, Robert, Leung, Helios T., Rogers, Julie, Bradshaw, Jeff, Stebbins, Mark, Leytze, Gina, Brady, William, Malacko, Alison R., Marquardt, Hans, Shaw, Shyh-Yu
Format: Article
Language:English
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Summary:CD28 and CTLA-4 are homologous T cell receptors of the immunoglobulin (Ig) superfamily, which bind B7 molecules (CD80 and CD86) on antigen-presenting cells and transmit important costimulatory signals during T cell activation. Here we have investigated the subunit structure of CTLA-4 and the stoichiometry of its binding to B7 molecules. We demonstrate CTLA-4 is a homodimer interconnected by one disulfide bond in the extracellular domain at cysteine residue 120. Each monomeric polypeptide chain of CTLA-4 contains a high affinity binding site for B7 molecules; soluble CTLA-4 and CD86 form complexes containing equimolar amounts of monomeric CTLA-4 and CD86 (i.e. a 2:2 molecular complex). Thus, CTLA-4 and probably CD28 have a receptor structure consisting of preexisting covalent homodimers with two binding sites. Dimerization of CTLA-4 and CD28 is not required for B7 binding, nor is it sufficient to trigger signaling.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.270.25.15417