One of the CD3ε subunits within a T cell receptor complex lies in close proximity to the Cβ FG loop

A recent crystal structure of the N15 α/β-T cell receptor (TCR) in complex with an Fab derived from the H57 Cβ-specific monoclonal antibody (mAb) shows the mAb fragment interacting with the elongated FG loop of the Cβ domain. This loop creates one side wall of a cavity within the TCR Ti- α/β constant region module (CαCβ) while the CD and EF loops of the Cα domain form another wall. The cavity size is sufficient to accommodate a single nonglycosylated Ig domain such as the CD3ε ectodomain. By using specific mAbs to mouse TCR-β (H57) and CD3ε (2C11) subunits, we herein provide evidence that only one of the two CD3ε chains within the TCR complex is located in close proximity to the TCR Cβ FG loop, in support of the above notion. Moreover, analysis of T cells isolated from transgenic mice expressing both human and mouse CD3ε genes shows that the heterologous human CD3ε component can replace the mouse CD3ε at this site. The location of one CD3ε subunit within the rigid constant domain module has implications for the mechanism of signal transduction throughout T cell development.