STRUCTURE OF THE T-CELL ANTIGEN RECEPTOR - EVIDENCE FOR 2 CD3 EPSILON-SUBUNITS IN THE T-CELL RECEPTOR CD3 COMPLEX

The T-cell antigen receptor (TCR) consists of heterodimeric glycoproteins (TCR αβ or γδ) that demonstrate homology with immunoglobulins. Noncovalently associated with the αβ (or γδ) heterodimer are at least five nonvariant proteins (CD3-γ, -δ, -ε, -ζ, and -η), which together comprise the TCR-CD3 complex. The stoichiometry of the antigen receptor has been assumed to be either αβγδεζζ or αβγδεζη. In this paper we provide several lines of evidence that support the notion that the mature TCR-CD3 complex on the cell surface contains two CD3-ε polypeptide chains. Transfection of two murine T cell-T cell hybridomas with the human DNA encoding CD3-ε protein demonstrated that both murine and human CD3-ε chains were present within the same TCR-CD3 complex. Analysis of thymocytes isolated from transgenic mice that expressed high copy numbers of the human CD3-ε gene showed that the heterologous human CD3-ε subunits were coexpressed with murine CD3-ε in the same TCR-CD3 complex. Since CD3-ε was shown to form disulfide-linked homodimers both in human and murine T cells, the two CD3-ε subunits present in the TCR-CD3 complex were in direct contact with one another. The presence of two CD3-ε polypeptide chains in close proximity to one another in the TCR-CD3 complex may have important implications for its assembly and its signal transduction mechanisms.