The zeta subunit of the T cell antigen receptor (TCR) exists primarily as a disulfide-linked homodimer. This receptor subunit is important in TCR-mediated signal transduction and is a substrate for a TCR-activated protein tyrosine kinase. The zeta chain was found to undergo ubiquitination in response to receptor engagement. This posttranslational modification occurred in normal T cells and tumor lines. Both nonphosphorylated and phosphorylated zeta molecules were modified, and at least one other TCR subunit, CD3 delta, was also ubiquitinated after activation of the receptor. These findings suggest an expanded role for ubiquitination in transmembrane receptor function.

The T cell antigen receptor is a multi-subunit receptor complex present on the surface of all mature and many developing T cells. It consists of clonotypic heterodimers noncovalently linked to five invariant chains that are encoded by four genes and referred to as the CD3 complex. The CD3 gamma, delta, and epsilon chains have been molecularly characterized. In this report the molecular cloning of a complementary DNA encoding the zeta chain of the murine T cell antigen receptor is described. The predicted protein sequence of the zeta chain suggests a structure distinct from those of any of the previously described receptor subunits.

The T-cell antigen receptor (TCR) is a multisubunit receptor complex specific to T cells subserving both antigen recognition and signal transduction functions. The { 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 coinmunoprecipitates 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 C. Using this as a probe, we have now isolated cDNAs encoding the human {. Sequence analysis of cDNAs encoding human and murine { 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' and 3' untranslated regions of the C mRNA. The previously characterized invariant 6, E, and y 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). Chas no sequence similarity to the CD3 chains and the localization of the human C gene to the centromeric region of chromosome 1 underscores the fact that it is a distinct genetic component of the TCR.Initiation of a normal immune response requires recognition of foreign antigen by T lymphocytes. This occurs when antigen-presenting cells bearing major histocompatibility complex (MHC) molecules bound with the appropriate antigen interact with T-cell receptors that recognize the MHCantigen complex as foreign. The T-cell antigen receptor (TCR) is a complex multisubunit structure whose components have been divided by both nomenclature and presumed function into two groups. The first group consists of the antigen recognition components of the receptor or Ti. On most T cells these components consist of a-j3 heterodimers, which are products of rearranged genes and are expressed in a clonally restricted manner (1-3). These clonotypic elements are immunoglobulin-like structures with constant and variable domains. The second group of receptor components are those that are constant in sequence for all T cells and are presumed to function primarily in signal transduction (4-11).The invariant 6, e, and y chains are collectively referred to as the CD3 complex. The members of the CD3 complex are related by amino acid sequence and are all members of the immunoglobulin gene superfamily (11-18). In addition, the CD3 components are all clustered within 300 kilobases (kb) of each other on human chromosome 11q23. The genes for the CD3 6 and y reside within 1.6 kb of each other (19-21).More recently, another invariant chain, ', has been discovered as part of the murine receptor complex (7). Although a (25,26). We have demonstrated that in human peripheral blood lymphocytes as in murine hybridomas this tyrosine kinase results in the tyrosine phosphorylation of ; with an increase in its apparent molecular mass from 16 to 21 kDa (27,...

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