Deletion of the cytoplasmic region of the CD3 epsilon subunit does not prevent assembly of a functional T-cell receptor.
The T-cell receptor (TCR) is a molecular complex comprised of a clonally restricted, immunoglobulin-like heterodimer (Ti), responsible for specific antigen recognition, and a set of monomorphic polypeptide CD3 subunits, termed gamma, delta, epsilon, zeta, and eta, presumed to be involved in transmembrane signaling events. To investigate the role of the CD3 epsilon subunit in signal transduction, we have transfected a murine hybridoma T-cell line with either wild-type or variant human CD3 epsilon cDNA that encodes a protein lacking 49 of the 55 cytoplasmic amino acid residues. Both wild-type and truncated CD3 epsilon human proteins assemble with endogenous murine CD3/Ti subunits to form functional surface TCRs: Anti-human CD3 epsilon monoclonal antibodies bind exclusively to these chimeric TCRs and trigger interleukin 2 production from the murine cells. Thus, the CD3 epsilon cytoplasmic domain is not required for assembly of the multimeric TCR. Furthermore, it is dispensable for the transduction of a stimulus delivered to the external part of the molecule, suggesting that interaction between the transmembrane and/or external regions of the other TCR chains is a prerequisite for transmembrane signaling.
Transy
C
C
Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, MA.
Moingeon
P
P
Stebbins
C
C
Reinherz
E L
EL
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics*; D015139:Blotting, Southern; D017252:CD3 Complex; D002460:Cell Line; D002872:Chromosome Deletion; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005796:Genes; D006801:Humans; D046911:Macromolecular Substances; D009154:Mutation; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D046911:Macromolecular Substances; D011948:Receptors, Antigen, T-Cell; D004247:DNA