Full T-cell activation critically depends on the engagement of the TCR (T-cell receptor) in conjunction with a second signal by co-stimulatory receptors that boost the immune response. In the present study we have compared signalling patterns induced by the two co-receptors CD2 and CD28 in human peripheral blood T-cells. These co-receptors were previously suggested to be redundant in function. By a combination of multi-parameter phosphoflow cytometry, phosphokinase arrays and Western blot analyses, we demonstrate that CD2 co-stimulation induces phosphorylation of the TCR-proximal signalling complex, whereas CD28 activates distal signalling molecules, including the transcription factors NF-κB (nuclear factor κB), ATF (activating transcription factor)-2, STAT3/5 (signal transducer and activator of transcription 3/5), p53 and c-Jun. These signalling patterns were conserved in both naïve and effector/memory T-cell subsets. We show that free intracellular Ca2+ and signalling through the PI3K (phosphoinositide 3-kinase)/Akt pathway are required for proper CD28-induced NF-κB activation. The signalling patterns induced by CD2 and CD28 co-stimulation lead to distinct functional immune responses in T-cell proliferation and cytokine production. In conclusion, CD2 and CD28 co-stimulation induces distinct signalling responses and functional outcomes in T-cells.
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Research Article|
May 29 2014
T-cell co-stimulation through the CD2 and CD28 co-receptors induces distinct signalling responses
Sigrid S. Skånland;
Sigrid S. Skånland
*Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo and Oslo University Hospital, N-0318 Oslo, Norway
†Biotechnology Centre, K. G. Jebsen Centre for Inflammation Research and K. G. Jebsen Centre for Cancer Immunotherapy, University of Oslo, N-0318 Oslo, Norway
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Kristine Moltu;
Kristine Moltu
*Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo and Oslo University Hospital, N-0318 Oslo, Norway
†Biotechnology Centre, K. G. Jebsen Centre for Inflammation Research and K. G. Jebsen Centre for Cancer Immunotherapy, University of Oslo, N-0318 Oslo, Norway
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Torunn Berge;
Torunn Berge
†Biotechnology Centre, K. G. Jebsen Centre for Inflammation Research and K. G. Jebsen Centre for Cancer Immunotherapy, University of Oslo, N-0318 Oslo, Norway
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Einar M. Aandahl;
Einar M. Aandahl
*Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo and Oslo University Hospital, N-0318 Oslo, Norway
†Biotechnology Centre, K. G. Jebsen Centre for Inflammation Research and K. G. Jebsen Centre for Cancer Immunotherapy, University of Oslo, N-0318 Oslo, Norway
§Section for Transplantation Surgery, Oslo University Hospital, N-0424 Oslo, Norway
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Kjetil Taskén
Kjetil Taskén
1
*Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo and Oslo University Hospital, N-0318 Oslo, Norway
†Biotechnology Centre, K. G. Jebsen Centre for Inflammation Research and K. G. Jebsen Centre for Cancer Immunotherapy, University of Oslo, N-0318 Oslo, Norway
‡Department of Infectious Diseases, Oslo University Hospital, N-0424 Oslo, Norway
1To whom correspondence should be addressed (email kjetil.tasken@ncmm.uio.no).
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Biochem J (2014) 460 (3): 399–410.
Article history
Received:
January 10 2014
Revision Received:
March 18 2014
Accepted:
March 25 2014
Accepted Manuscript online:
March 25 2014
Citation
Sigrid S. Skånland, Kristine Moltu, Torunn Berge, Einar M. Aandahl, Kjetil Taskén; T-cell co-stimulation through the CD2 and CD28 co-receptors induces distinct signalling responses. Biochem J 15 June 2014; 460 (3): 399–410. doi: https://doi.org/10.1042/BJ20140040
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