Most anti-human CD3 monoclonal antibodies are directed to the CD3 epsilon subunit.
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.
Transy
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C
Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, MA 02115.
Moingeon
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PE
Marshall
B
B
Stebbins
C
C
Reinherz
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EL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D017252:CD3 Complex; D002460:Cell Line; D000939:Epitopes / Q000032:analysis; D006801:Humans; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D000939:Epitopes; D011948:Receptors, Antigen, T-Cell