International Immunology Advance Access published online on May 17, 2004
International Immunology, doi:10.1093/intimm/dxh098
© 2004 by The Japanese Society for Immunology
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1 Malaghan Institute of Medical Research, Wellington, New Zealand
* To whom correspondence should be addressed. E-mail: tbackstrom{at}malaghan.org.nz.
A key question yet to be resolved concerns the structure and function relationship of the TCR complex. How does antigen recognition by the TCR- Keywords:
Keywords: antigen signaling, structure-function, T cell receptor
Accepted April 19, 2004
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A chimeric T cell receptor with super-signaling properties
2 Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
3 Laboratory of Transplantation Immunology and Nephrology, Department of Research, University Hospital Basel, CH-4031 Basel, Switzerland
Abstract 
chains result in the activation of distinct signal transduction pathways by the CD3-
/
complex? To investigate which part of the TCR- chain is involved in TCR signaling, we exchanged different domains of the constant regions of the TCR- chain with the corresponding TCR- chain domains. We show here that hybridoma cells expressing a chimeric TCR- chain (III) containing intracellular and transmembrane TCR- amino acids, together with a wild-type TCR- (wt) chain, were 10 times more sensitive to antigenic stimulation compared to cells expressing TCR-wt/wt chains. This super-signaling phenotype of the III chain was observed in two different TCRs. One specific for an alloantigen (I-Abm12) and one for an autoantigen (I-Ab/MOG35-55). We found that this chimeric wt/III TCR had normal association with CD3- and chains. To investigate the effect of the chimeric III chain in transgenic T cells, we made MOG35-55-specific TCR transgenic mice expressing either the wt/wt or chimeric wt/III TCR. Similar to what was observed in hybridoma cells, transgenic wt/III T cells showed a super-signaling phenotype upon antigenic stimulation. Further studies may help us understand the effect of increased TCR signaling on autoimmunity and may lead to the identification of signaling molecules that can be targeted to stop the progression of autoimmune disorders such as multiple sclerosis.
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