his.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
A Theoretical Framework for Quantitative Analysis of the Molecular Basis of Costimulation
University of Skövde, School of Life Sciences.
Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom.
Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, United Kingdom.
University of Skövde, School of Life Sciences.
Show others and affiliations
2005 (English)In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 175, no 3, 1575-1585 p.Article in journal (Refereed) Published
Abstract [en]

We present a theoretical framework for simulating the synaptic accumulation of the costimulatory molecules CD28, CTLA-4, B7-1, and B7-2, based on a system of mean-field, ordinary differential equations, and rigorous biophysical and expression data. The simulations show that binding affinity, stoichiometric properties, expression levels, and, in particular, competition effects all profoundly influence complex formation at cellular interfaces. B7-2 engages 33-fold more CD28 than CTLA-4 at the synapse in contrast to B7-1, which ligates ~7-fold more CTLA-4 than CD28. Although B7-1 completely dominates interactions with CTLA-4, forming linear arrays of 7-18 receptor-ligand pairs, CTLA-4 is fully engaged by B7-2 when B7-1 is absent. Additional simulations reveal the sensitivity of CD28 interactions to modeled transport processes. The results support the concept that B7-2 and B7-1 are the dominant ligands of CD28 and CTLA-4, respectively, and indicate that the inability of B7-2 to recruit CTLA-4 to the synapse cannot be due to the differential binding properties of B7-1 and B7-2 only. We discuss the apparent redundancy of B7-1 in the context of a potentially dynamic synaptic microenvironment, and in light of functions other than the direct enhancement of T cell inhibition by CTLA-4.

Place, publisher, year, edition, pages
American Association of Immunologists , 2005. Vol. 175, no 3, 1575-1585 p.
National Category
Natural Sciences
Research subject
Natural sciences
Identifiers
URN: urn:nbn:se:his:diva-1627ISI: 000233648000027PubMedID: 16034096Scopus ID: 2-s2.0-22544465538OAI: oai:DiVA.org:his-1627DiVA: diva2:31903
Available from: 2007-08-03 Created: 2007-08-03 Last updated: 2013-04-09Bibliographically approved

Open Access in DiVA

No full text

Other links

PubMedScopushttp://www.jimmunol.org/cgi/content/full/175/3/1575

Search in DiVA

By author/editor
Jansson, AndreasHarlén, MikaelNilsson, Patric
By organisation
School of Life Sciences
In the same journal
Journal of Immunology
Natural Sciences

Search outside of DiVA

GoogleGoogle Scholar

Altmetric score

Total: 784 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf