THE T-CELL RECEPTOR ALPHA-BETA V-J SHUFFLING SHOWS LACK OF AUTONOMY BETWEEN THE COMBINING SITE AND THE CONSTANT DOMAIN OF THE RECEPTOR CHAINS

In order to assess the structural independence of the T cell receptor (TCR) combining site from the rest of the molecule we have generated two recombinant chains consisting of a TCR V-J alpha region linked to the Cbeta and a TCR V-J beta linked to the Calpha. If the V and C domains of the TCR form independent domains, as has been shown for the Ig molecules, we would expect to obtain a functional chimeric TCR. Interestingly, it was found that the shuffled molecules are produced intracellularly in T cell hybridomas, but are not expressed on the cell surface. To explain this failure of the shuffled molecules we propose that the TCR has a more compact structure, compared to the Ig, and that it is indispensable to keep a longitudinal inter-domain contact between the V-J and C portion to have a functional molecule.