Role of CD3 /in T Cell Receptor Assembly

The T cell receptor (TCR) consists of the Tiot(3 heterodimer and the associated CD378E and ge chains. The structural relationships between the sub- units 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) do- main of CD37 in assembly and cell surface expression of the complete TCR in human T cells. A computer model indicated that the EC domain of CD37 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~/. Site-directed mutagenesis demonstrated that these sites play a crucial role in TCR assembly probably by binding to CD3e. Mutagenesis of N-linked glycosylation sites showed that glycosylation of CD3~ is not required for TCR assembly and expres- sion. In contrast, treatment of T cells with tunicamycin suggested that N-linked glycosylation of CD38 is re- quired for TCR assembly. Site-directed mutagenesis of the acidic amino acid in the TM domain of CD3~/dem- onstrated that this residue is involved in TCR assembly probably by binding to Ti13. Deletion of the entire CY domain of CD3~/did not prevent assembly and expres- sion of the TCR. In conclusion, this study demonstrated that specific TCR interaction sites exist in both the EC and TM domain of CD3% Furthermore, the study indi- cated that, in contrast to CD3q¢, glycosylation of CD38 is required for TCR assembly and expression.