Molecular Cloning and Chromosomal Localization of the Human T-Cell Receptor ζ Chain: Distinction from the Molecular CD3 Complex

The T-cell antigen receptor (TCR) is a multisubunit receptor complex specific to T cells subserving both antigen recognition and signal transduction functions. The ζ chain of the TCR is a component of all surface receptor complexes. This chain was first identified in murine T cells by virtue of the fact that it coimmunoprecipitates with the TCR complex using antibodies directed against either the clonespecific subunits or invariant CD3 subunits of the receptor. Recently, we have isolated a cDNA encoding the murine ζ. Using this as a probe, we have now isolated cDNAs encoding the human ζ. Sequence analysis of cDNAs encoding human and murine ζ reveals that it is a highly conserved protein. In addition to amino acid homology, there is remarkable interspecies conservation in the nucleotide sequence of the 5\u27 and 3\u27 untranslated regions of the C mRNA. The previously characterized invariant �, ε, and γ chains of the TCR, referred to as the CD3 complex, share significant sequence and structural homology with each other and are all located within 300 kilobases of each other on human chromosome 11 (11q23). ζ has no sequence similarity to the CD3 chains and the localization of the human ζ gene to the centromeric region of chromosome 1 underscores the fact that it is a distinct genetic component of the TCR