Stimulation of T cells by antigen activates many signalling pathways. The capacity for this range of biochemical responses may reside in the complex structure of the seven-chain T-cell antigen receptor (TCR). In addition to the complexity shared by all TCRs, coexpression of zeta (zeta) and the distinct but related eta (eta) chains creates structural diversity among the TCR complexes expressed on a given cell. In most murine T cells that we have studied, about 90% of the heptameric receptor complexes contain a zeta zeta disulphide homodimer, whereas 10% contain a zeta eta disulphide heterodimer. Recent studies suggest that zeta has a critical role in allowing antigen to activate the cell, whereas eta expression has been correlated with the capacity for antigen-induced phosphoinositide turnover. A third zeta-related protein, the gamma (gamma) chain of the Fc epsilon and some Fc gamma receptors, exists as a disulphide homodimer in those complexes. The structural relatedness of zeta and gamma is emphasized by the recent demonstration of zeta zeta in association with CD16 in TCR-negative natural killer cells. Here we identify T cells lacking Fc receptors but coexpressing zeta, gamma, and eta, document the formation of novel heterodimers between zeta and gamma and between eta and gamma and show their association with the TCR. A greater range of homologous coupling structures than previously thought may be one way of achieving the variety of TCR-mediated (and possibly Fc receptor-mediated) biochemical responses and effector functions.

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,...

A clone for the iron-responsive element (IRE)-binding protein (IRE-BP) has been transfected and expressed in mouse fibroblasts. The IRE-BP gene product binds IREs with high affinity and specificity. Amino acid alignments reveal that the IRE-BP is 30% identical to mitochondrial aconitase. The 18 active site residues of mitochondrial aconitase are identical to those in the IRE-BP, suggesting that the IRE-BP may possess aconitase activity. After purification of native IRE-BP and immunoaffinity purification of transfected and expressed IRE-BP, we demonstrate that the purified IRE-BP has aconitase activity.