Stevens, C.N.; (2009) The interferon alpha receptor utilises T-cell receptor-associated proteins for signalling. Doctoral thesis , UCL (University College London).

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Abstract

The interferon alpha receptor (IFNAR) and T-cell receptor (TCR) are expressed upon the T-cell surface. The dimeric Class I interferon receptor is a cytokine receptor that recognises interferons such as IFNα. Interferons (IFNs) are pluripotent, antiviral cytokines that causes antiproliferative effects, primarily through Jak/STAT signalling. The T-cell receptor is an antigenic receptor that recognises antigenically-derived peptides in the context of the MHC complex located on an antigen presenting cell, resulting in a cellular proliferation. Although both receptors elicit opposing cellular outcomes, both the TCR and IFNAR activate the ERK MAPK signalling pathway, albeit with a different time course. Furthermore, studies have shown that the IFNAR and TCR utilise an overlapping subset of proteins for this pathway to occur such as CD45, Lck and Zap70. In this study evidence is presented to show that two further TCR-associated proteins are phosphorylated in response to the IFNAR; the 95kDa guanosine nucleotide exchange factor, Vav, and the 76kDa adaptor protein Slp76. This proceeds in a similar manner to that observed at the TCR. Furthermore, the absence of either protein impairs IFNAR-induced ERK MAPK signalling. The similarities between TCR and IFNAR signalling led to questioning of whether crosstalk occurs between the two receptors. To address this possibility a TCRβ deficient cell line, which lacks functional TCR expression, was utilised. It was demonstrated that the absence of the TCR completely abrogates the ERK MAPK response emanating from the IFNAR yet Jak/STAT signalling is unaffected. These results highlight for the first time an intimate connection between the TCR and IFNAR.

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