J. Exp. Med., Volume 187, Number 9, May 4, 1998 1529-1536

One of the CD3 Subunits within a T Cell Receptor Complex Lies in Close Proximity to the C FG Loop

By Yoseph Ghendler, Alex Smolyar, Hsiu-Ching Chang, and Ellis L. Reinherz

From the Laboratory of Immunobiology, Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115

A recent crystal structure of the N15 /-T cell receptor (TCR) in complex with an Fab derived from the H57 C-specific monoclonal antibody (mAb) shows the mAb fragment interacting with the elongated FG loop of the C domain. This loop creates one side wall of a cavity within the TCR Ti-/ constant region module (CC) while the CD and EF loops of the C domain form another wall. The cavity size is sufficient to accommodate a single nonglycosylated Ig domain such as the CD3 ectodomain. By using specific mAbs to mouse TCR- (H57) and CD3 (2C11) subunits, we herein provide evidence that only one of the two CD3 chains within the TCR complex is located in close proximity to the TCR C FG loop, in support of the above notion. Moreover, analysis of T cells isolated from transgenic mice expressing both human and mouse CD3 genes shows that the heterologous human CD3 component can replace the mouse CD3 at this site. The location of one CD3 subunit within the rigid constant domain module has implications for the mechanism of signal transduction throughout T cell development.

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