MOLECULAR-CLONING OF THE CD3-ETA-SUBUNIT IDENTIFIES A CD3-ZETA-RELATED PRODUCT IN THYMUS-DERIVED CELLS

The CD3η subunit of the T-cell antigen receptor forms a heterodimeric structure with the CD3ζ subunit in thymus-derived lymphoid cells and is apparently involved in signal transduction through the receptor. Here we report the primary structure of murine CD3η as deduced from protein microsequencing and cDNA cloning. The mature protein is divided into three domains: a 9-amino acid extracellular segment, a 21-amino acid transmembrane segment including a negatively charged residue characteristic of CD3 subunits, and a 155-amino acid cytoplasmic tail. The NH2-terminal sequences of CD3η and CD3ζ are identical through amino acid 122 of each mature protein but then diverge in the remainder of their respective COOH-terminal regions, consistent with alternatively spliced products of a common gene. The cytoplasmic domain of CD3η is 42 amino acids larger than that of CD3ζ but lacks one of six potential tyrosine phosphorylation sites as well as a putative nucleotide binding site previously identified in CD3ζ. These structural features presumably account for the difference between CD3η and CD3ζ function and are consistent with the notion that CD3η may be an important component of a T-cell receptor isoform(s) during thymic development.