The interchain disulfide linkage is not a prerequisite but enhances CD28 costimulatory function

Eszter Lazar-Molnar, Steven C. Almo, Stanley G. Nathenson

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Oligomeric state makes important contributions to the signaling mechanisms of costimulatory molecules. In this study we address the biological relevance of the disulfide-linked dimeric structure of CD28. Fluorescence Resonance Energy Transfer (FRET) demonstrates that removal of the interdomain disulfide bond (C123) does not interfere with the formation of CD28 oligomers on the cell surface. Although the C123S mutant shows 40% lower binding affinity to the ligand B7-1, it is able to costimulate anti-CD3-induced IL-2 production but at a lower level (150%) compared to the wild-type (270%). Interestingly, binding to B7-2 was not affected. Thus, the covalently linked dimeric structure of CD28 represents an important mechanistic determinant for the optimal costimulatory activity in the immunological synapse.

Original languageEnglish (US)
Pages (from-to)125-129
Number of pages5
JournalCellular Immunology
Volume244
Issue number2
DOIs
StatePublished - Dec 2006

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Disulfides
CD80 Antigens
Immunological Synapses
Fluorescence Resonance Energy Transfer
Interleukin-2

Keywords

  • B7-1
  • CD28
  • Costimulatory
  • Dimer
  • Disulfide
  • FRET
  • Oligomerization

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

Cite this

The interchain disulfide linkage is not a prerequisite but enhances CD28 costimulatory function. / Lazar-Molnar, Eszter; Almo, Steven C.; Nathenson, Stanley G.

In: Cellular Immunology, Vol. 244, No. 2, 12.2006, p. 125-129.

Research output: Contribution to journalArticle

Lazar-Molnar, Eszter ; Almo, Steven C. ; Nathenson, Stanley G. / The interchain disulfide linkage is not a prerequisite but enhances CD28 costimulatory function. In: Cellular Immunology. 2006 ; Vol. 244, No. 2. pp. 125-129.
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