ONE OF THE CD3-EPSILON SUBUNITS WITHIN A T-CELL RECEPTOR COMPLEX LIESIN CLOSE PROXIMITY TO THE C-BETA FG LOOP

A recent crystal structure of the N15 alpha/beta-T cell receptor (TCR) in complex with an Fab derived from the H57 C beta-specific monoclona l antibody (mAb) shows the mAb fragment inter acting with the elongate d FG loop of the C beta domain. This loop creates one side wall of a c avity within the TCR Ti-alpha/beta constant region module (C alpha C b eta) while the CD and EF loops of the C alpha domain form another wall . The cavity size is sufficient to accommodate a single nonglycosylate d Ig domain such as the CD3 epsilon ectodomain. By using specific mAbs to mouse TCR-beta (H57) and CD3 epsilon (2C11) subunits, we herein pr ovide evidence that only one of the two CD3 epsilon chains within the TCR complex is located in close proximity to the TCR C beta FG loop, i n support of the above notion. Moreover, analysis of T cells isolated from transgenic mice expressing both human and mouse CD3 epsilon genes shows that the heterologous human CD3 epsilon component can replace t he mouse CD3 epsilon at this site. The location of one CD3 epsilon sub unit within the rigid constant domain module has implications for the mechanism of signal transduction throughout T cell development.