Transy C, Moingeon P E, Marshall B, Stebbins C, Reinherz E L
Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, MA 02115.
Eur J Immunol. 1989 May;19(5):947-50. doi: 10.1002/eji.1830190525.
The T cell receptor is a molecular complex compriSed of a clonally-restricted heterodimer (Ti) responsible for specific antigen recognition and a set of invariant CD3 peptides termed gamma, delta, epsilon, zeta and eta. The latter are believed to be involved in transmembrane signaling events given that monoclonal antibodies (mAb) directed to the native CD3 structure can trigger T cell activation. We show here that the vast majority of anti-human CD3 mAb are directed to an epitope(s) encoded in part or in total by the epsilon subunit since 15 of 18 independent mAb specifically react with a murine T cell line expressing the human CD3 epsilon chain at its cell surface. The WT31 mAb is also reactive with this cell line showing that its target epitope, originally assigned to the Ti structure, rather maps to the CD3 epsilon subunit. These findings suggest that the CD3 epsilon subunit is the most exposed of the native CD3 structures which are immunogenic and that cross-linking of the CD3 epsilon chain by mAb mediates the subsequent T cell activation via the T cell receptor complex.
T细胞受体是一种分子复合物，由负责特异性抗原识别的克隆限制性异二聚体（Ti）和一组称为γ、δ、ε、ζ和η的恒定CD3肽组成。鉴于针对天然CD3结构的单克隆抗体（mAb）可触发T细胞活化，后者被认为参与跨膜信号传导事件。我们在此表明，绝大多数抗人CD3 mAb针对的表位部分或全部由ε亚基编码，因为18个独立的mAb中有15个与在细胞表面表达人CD3ε链的小鼠T细胞系特异性反应。WT31 mAb也与该细胞系反应，表明其靶表位最初被指定为Ti结构，而实际上位于CD3ε亚基上。这些发现表明，CD3ε亚基是天然CD3结构中最易暴露且具有免疫原性的结构，mAb对CD3ε链的交联通过T细胞受体复合物介导随后的T细胞活化。
