Title : Role of CD3 gamma in T cell receptor assembly
Abstract :
The T cell receptor ( TCR ) consists of the Ti alpha beta heterodimer and the associated CD3 gamma delta epsilon and zeta 2 chains
The structural relationships between the subunits of the TCR complex are still not fully known
In this study we examined the role of the extracellular (EC), transmembrane (TM), and cytoplasmic (CY) domain of CD3 gamma in assembly and cell surface expression of the complete TCR in human T cells
A computer model indicated that the EC domain of CD3 gamma folds as an Ig domain
Based on this model and on alignment studies, two potential interaction sites were predicted in the EC domain of CD3 gamma
Site-directed mutagenesis demonstrated that these sites play a crucial role in TCR assembly probably by binding to CD3 epsilon
Mutagenesis of N-linked glycosylation sites showed that glycosylation of CD3 gamma is not required for TCR assembly and expression
In contrast, treatment of T cells with tunicamycin suggested that N-linked glycosylation of CD3 delta is required for TCR assembly
Site-directed mutagenesis of the acidic amino acid in the TM domain of CD3 gamma demonstrated that this residue is involved in TCR assembly probably by binding to Ti beta
Deletion of the entire CY domain of CD3 gamma did not prevent assembly and expression of the TCR
In conclusion, this study demonstrated that specific TCR interaction sites exist in both the EC and TM domain of CD3 gamma
Furthermore, the study indicated that, in contrast to CD3 gamma , glycosylation of CD3 delta is required for TCR assembly and expression