Failure to synthesize the CD3-γ chain. Consequences for T cell antigen receptor assembly, processing, and expression

Abstract

The TCR consists of the Ti αβ heterodimer and the associated CD3 chains, CD3 γ δ ε zeta 2 or zeta eta. The structural relationships between the subunits of the Ti/CD3 complex are still not fully understood. To explore the roles of the individual CD3 chains for the assembly, intracellular processing, and expression of the TCR, mutants of the T cell line Jurkat were isolated. One variant, JGN, was found to produce all the Ti/CD3 components with the exception of CD3-γ. The results indicate that: 1) the tetrameric form (Ti αβ-CD3 δ ε) of the Ti/CD3 complex is produced in the endoplasmic reticulum in the absence of CD3-γ; 2) CD3-zeta does not associate with the Ti αβ-CD3 δ ε complex; 3) the Ti αβ-CD3 δ ε complex is not exported from the endoplasmic reticulum to the Golgi apparatus; and 4) CD3-γ is required for cell surface expression of the Ti/CD3 complex. Transfection of the wild-type CD3-γ gene into JGN reconstituted expression of functional Ti/CD3 complexes, and analysis of T cell lines producing different amounts of CD3-γ indicated that CD3-γ and CD3-δ competed for the binding to CD3-ε.