The T cell receptor/CD3 complex is composed of at least two autonomous transduction modules

Abstract

SummaryReeent studies have demonstrated that the CD3-~ subunlt of the T eell antigen reeeptor (TCR) eomplex Is involved In signal transduetlon. However, the funetlon of the remalnlng Invariant subunits, CD3-y, -ö, and e, Is still poorly understood. To examine thelr role In TCR funetlon, we have eonstrueted TCR/CD3 eomplexes devold of tunetlonal ~ subunlt and showed that they are still able to trigger the produellon of Interleukln-2 in response to antigen or superantigen. These data, together with previous results, Indleate that the TCR/ CD3 eomplex Is eomposed of at least two parallel Iransduelng unlts, made 01 the YÖE and ~ ehalns, respeetlvely, Furthermore, the analysis 01 partially truneated ~ ehains has led us to Indlvlduallze a lunetlonal domaln that may have eonstltuted the buildlng block of most of the transduelng subunlts assoelated wlth antigen reeeptors and some Fe receptors. IntroduetionThe T cell antigen receptor (TCR) is a multisubunit complex composed of the products of at least six distinct genes. The TCR a and TCR ß subunits exist as disulfidelinked heterodimers, possess short cytoplasmic tails, and contain clonally variable regions that determine the antigenic specificity of the complex. The remaining subunits, termed CD3-y, -ö, -E, -~, and -1], are invariant, noncovalently associated with the TCR aß dimer, and possess large intracytoplasmic domains thought to be responsible for coupling antigen recognition to various signal transductlon pathways. The evolutionarily related y, Ö, and e subunits are expressed as noncovalently associated ye and OE pairs (Koning et al., 1990;Blumberg et al. , 1990; De la Herra et al. , 1991), and display immunoglobulin-like extracellular domains (Gold et al., 1987). In contrast, the ~ and 1] subunlts contaln an extracellular domain of only 9 residues and constitute the prototype of a new protein family that includes the y chain of the high affinity IgE receptor (FceRI)

CD3 gamma contains a phosphoserine-dependent di-leucine motif involved in down-regulation of the T cell receptor.

“…the chimeras (Letourneur and Klausner, 1992b (Reth, 1989;Wegener et al, 1992). This motif has been found to be critical for signal transduction by the CD3e and r chains (Letourneur and Klausner, 1992a;Wegener et al, 1992;A.-M.K.Wegener and B.Malissen, unpublished data), and probably plays a similar role in CD3-y.…”

“…The disulfide-linked ca3 heterodimer is responsible for antigen recognition (Dembic et al, 1986;Saito et al, 1987b) and the activation signals are delivered through the associated CD3 chains (Malissen and Schmitt-Verhulst, 1993). Recent studies have provided definitive evidence for a signal transduction function of the CD3E and r chains Romeo and Seed, 1991;Letourneur and Klausner, 1992a;Wegener et al, 1992;Hermans and Malissen, 1993); however, the specific role of the CD3-y and 6 chains in TCR function is still unknown. After TCR stimulation, a number of cellular proteins become phosphorylated on tyrosine residues, among them being r (Baniyash et al, 1988), ZAP-70 (Chan et al, 1991), the proto-oncogene vav (Margolis et al, 1992) and phospholipase C-yl (PLC'yl) (Park et al, 1991;Secrist et al, 1991;Weiss et al, 1991).…”

New simplified molecular design for functional T cell receptor

“…The polymerase chain reaction (PCR) was used to amplify a cDNA segment encoding for the cytoplasmic und transmembrane region of the murine CD35 chain and 42 amino acids of the hinge region of murine CD8a (oligonucleotide primers 5451,5452). As a template for this reaction we used the plasmid CDS5 [6]. The primers of this reaction contained a SalI and a HindIII restriction site so that the amplified PCR product could be cloned after digestion with SalI and HindIII into the SalI-Hind111 opened pHfiAPr-1-neo(RI).…”

Purification and Characterization of Human ZAP-70 Protein-tyrosine Kinase from a Baculovirus Expression System

“…The ITAM, first noted by Reth (13), is found in three copies in the TCR chain and in one copy each in the CD3␥, ␦, and ⑀ chains (1,(13)(14)(15)(16)(17). The presence of ITAM cytoplasmic sequence in chimeric receptors has been shown to be sufficient to permit T cell activation following receptor cross-linking (14,15,22).…”