Disease relevance of Cd3e

• A cell line derived from a RAG-1 x p53 double mutant thymic lymphoma expressed low levels of CD3-epsilon, -gamma, and -delta on the surface [1].
• Bone marrow (BM) cells from a child with an immature (CD3-) acute T lymphoblastic leukemia (T-ALL) bearing no chromosomal abnormalities failed to grow in long-term culture in the presence or absence of recombinant human (rh) growth factors but could be engrafted in severe combined immunodeficient (SCID) mice and induced leukemia [2].
• The significance of pTAC12 dimer in the CD3 complex of immature thymocytes in vivo was demonstrated by coprecipitation of pTAC12 with the CD3 complex in thymocytes from SCID mice [3].
• Recent studies in a mouse model indicate that anti-mouse CD3 Abs with low affinity for Fc receptors can achieve immunosuppression without T cell activation, toxicity, or an anti-Ab response [4].
• With the goal of investigating their structure, Escherichia coli expression was utilized to produce CD3 ectodomain fragments including the murine CD3epsilon subunit N-terminal Ig-like extracellular domain alone or as a single chain construct with that of CD3gamma [5].

Psychiatry related information on Cd3e

• We have produced bispecific antibodies, directed against the surface-expressed Id of the mouse BCL1 lymphoma and the mouse CD3 complex, by hybrid-hybridoma fusion [6].
• We monitored the evolution of thymocyte populations containing prelymphoma cells during the latency period, using CD3 and TL as markers, in a transfer assay [7].

High impact information on Cd3e

• Even when T cell activation finally overrides regulation, stimulation of regulatory cells by CD3 antibodies may reset the control of autoimmunity [8].
• The pre-T cell receptor (pre-TCR) that minimally consists of the TCR beta chain and the disulfide-linked pre-T cell receptor alpha (pT alpha) chain in association with signal-transducing CD3 molecules rescues from programmed cell death cells with productive TCR beta rearrangements [9].
• The T cell receptor/CD3 complex: a dynamic protein ensemble [10].
• Recruitment of Nck by CD3 epsilon reveals a ligand-induced conformational change essential for T cell receptor signaling and synapse formation [11].
• The T cell receptor complex (TCR-CD3) is composed of TCR alpha/beta ligand binding subunits bound to the CD3 subunits responsible for signal transduction [11].

Chemical compound and disease context of Cd3e

• To investigate whether CsA inhibits only the cell death through the signals via the TCR/CD3 complex or all of the programmed cell death induced by various reagents, we further established CD4+8+ thymic lymphomas which result in programmed cell death after activation with calcium ionophore, dexamethasone, cyclic AMP or anti-CD3 antibody [12].
• The influence of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure on the cytokine-dependent toxicity syndrome induced by the injection of 145-2C11 (anti-CD3), a hamster monoclonal antibody to the CD3 epsilon portion of the murine T-cell receptor, was studied [13].
• Parenteral administration of CD3-specific monoclonal antibody is an approved therapy for transplantation in humans and is effective in autoimmune diabetes [14].
• Paradoxically, CD3 cross-linking prior to TCR stimulation results in apoptotic cell death, as does injection of anti-CD4 antibodies in vivo of CD4 ligation by HIV glycoprotein (gp) 120 [15].
• Lewis lung carcinoma cell adhesion to CD3 monolayers was accompanied by an enhanced 12(S)-HETE biosynthesis by tumor cells, which paralleled the tumor cell-induced endothelial cell retraction in a cell number-dependent manner [16].

Biological context of Cd3e

• An analysis of CD3- and CD28-induced signal transduction revealed reduced ERK and JNK enzyme activities in murine anergic T cells [17].
• Using insertional mutagenesis and inverse-PCR, we show that B-cell leukemia development in the E2a-PBX1 x CD3epsilon(-/-) compound transgenic animals is significantly accelerated when compared to control littermates, and document several known and novel integrations in these tumors [18].
• Likewise, antibody coligation of CD3 and CD4 results in an agonist-like phosphorylation pattern, whereas bivalent engagement of CD3 alone gives a partial agonist-like pattern [19].
• In this study, we examined the role of CD3straightepsilon ITAM-mediated signals in T cell development by genetically reconstituting CD3 epsilon-deficient mice with transgenes encoding either wild-type or ITAM-mutant (signaling defective) forms of the protein [20].
• Furthermore, the enhanced signaling in CD4(+)CD8(+) double positive thymocytes appears to be compensated by the selective down-regulation of CD3 on mature thymocytes and peripheral T cells from both strains of mutant c-Cbl mice [21].

Anatomical context of Cd3e

• The L-CA- T cell clones failed to proliferate in response to antigen or cross-linked CD3; however, they could still proliferate in response to IL-2 [22].
• Here we identify a new TCR isoform expressed on splenic CD2+, CD3/Ti alpha-beta+, CD4-, CD8-, CD16+, NK1.1+ mouse large granular lymphocytes (LGL), which are devoid of CD3 zeta and CD3 eta proteins [23].
• TCR-alpha x p53 double mutant cell lines were found to express complexes consisting of TCR-beta chains associated with CD3-epsilon, -gamma, and -delta chains and CD3-zeta zeta dimers [1].
• Single CD8(+) CD44(low) lymph node T cells were activated to divide at high frequency with IL-2 and immobilized antibodies to CD3, CD8, and LFA-1 [24].
• Remarkably, this is not an ITAM in the TCR/CD3 complex because this is not expressed by this T cell hybridoma [25].

Associations of Cd3e with chemical compounds

• To examine the proximal signaling processes mediated by the pre-TCR complex and the role of the TCR-zeta chain in these processes, we stimulated pre-TCR-expressing cells and analyzed the interactions of the TCR/CD3 invariant chains with the Syk/ZAP-70 family of protein tyrosine kinases [26].
• The requirement for retinol in CD3-mediated T cell activation cannot be satisfied by retinoic acid or ILs-1, 2, 4, and 6, and tumor necrosis factor-alpha whereas interferon gamma can substitute for retinol [27].
• The CD3epsilon proline-rich sequence, and its interaction with Nck, is not required for T cell development and function [28].
• In a mouse strain termed E delta P, a neomycin cassette inserted within the CD3 epsilon promoter abolishes CD3 epsilon and delta expression and also abolishes CD3 gamma expression in all but a small minority (< or =1%) of prothymocytes [29].
• The T cell receptor (TcR) consists of two disulfide-linked glycoprotein chains (alpha/beta or gamma/delta) and is noncovalently associated with a group of small and invariable CD 3 proteins [30].

Physical interactions of Cd3e

• Pull-down experiments demonstrated the inability of Nck to bind to the CD3epsilon PRS in thymocytes from mutant mice after TCR ligation [28].
• To investigate the molecular bases for the dichotomies between naive and memory CD4 T cells and to understand how the T cell receptor (TCR) directs diverse functional outcomes, we investigated proximal signaling events triggered through the TCR/CD3 complex in naive and memory CD4 T cell subsets isolated on the basis of CD45 isoform expression [31].
• Resting murine T cell activation induced by either CD3 complexes or Thy1 molecules was investigated in vitro, using surface-bound anti-CD3 mAb as the stimulus [32].
• The TCR/CD3 complex remained intact on peripheral T cells except in mice treated with flt3-L where CD3-zeta loss was observed [33].
• CD3 signaling leads to an early induction of NFAT1-P1 complexes correlating with a strong induction of the IL-4 gene [34].

Enzymatic interactions of Cd3e

• Lck and FynT are postulated to initiate TCR-triggered signal transduction by phosphorylating the CD3 and zeta subunits of the TCR complex [35].
• Recruitment of ZAP-70 protein tyrosine kinase to the T cell antigen receptor (TCR) is mediated by the binding of the SH2 domains of this enzyme to phosphorylated ITAM motifs in the CD3 and TCRzeta subunits [36].

Co-localisations of Cd3e

• Confocal microscopy using fluorescent anti-TCR mAb showed that after 15 min the TCR/CD3 complex colocalized with the transferrin receptor within endosomes, whereas at later times (2 h) it migrated in late endocytic compartments devoid of transferrin receptor [37].

Regulatory relationships of Cd3e

• We have determined whether in vivo administration of monoclonal antibodies (mAbs) directed at the T-cell surface protein CD3 induces T-cell responsiveness to IL-2, stimulates cytolytic molecular programs of natural killer cells and cytotoxic T cells, and induces tumor regression [38].
• Second, Cbl-deficient thymocytes expressed CD3 and CD4 molecules at higher levels, which consequently may increase the avidity of TCR/major histocompatibility complex/coreceptor interaction [39].
• These data indicate that signals resulting from exclusive CD3 engagement can influence CD8 molecular associations and activate CD8-bound p56(lck) [40].
• Lck dependence of signaling pathways activated by gamma-irradiation and CD3 epsilon engagement in RAG-1(-/-)-immature thymocytes [41].
• These results suggest a role for CD30 in regulating the onset of apoptosis in CD8 T cells after interruption of CD3/TCR [42].

Gene context of CD3e

• Lymphocytes of mouse strains BALB/c and STS/A stimulated by antiCD3e mAb (KT3 [43] differ in proliferative response [44]. This strain difference is controlled by polymorphism in gene Fcgr2 (Fcgamma receptor 2/CD32) [45] and by loci Tria1 (T cell receptor induced activation 1) on mouse chromosome 11 [46], Tria2 (chromosome 15 in the vicinity of myc ) [46], Tria3 (chromosome 17 ) [47], Tria4 (chromosome 7) [48] and by Tria5 (chromosome 9 ) [48].

Other interactions of Cd3e

• Interleukin 2-mediated uncoupling of T cell receptor alpha/beta from CD3 signaling [49].
• The NK1.1+ T cells from wild-type and CD3 zeta-deficient mice had equal levels of CD3 expression [50].
• At a molecular level, they express the pre-T cell receptor alpha (pT alpha) gene, CD3-gamma, CD-delta and CD-epsilon, and RAG-1 recombination enzyme and have initiated rearrangements in the T cell receptor (TCR)-beta locus (D-J) [51].
• Restoration of early thymocyte differentiation in T-cell receptor beta-chain-deficient mutant mice by transmembrane signaling through CD3 epsilon [52].
• Coaggregation of CD3 and CD4 reconstituted this Lck-dependent signaling pathway in Fyn(-/-) T cells [53].

Analytical, diagnostic and therapeutic context of Cd3e

• Moreover, ligation of the TCR expressed on thymocytes from Lck-deficient mice largely failed to induce the phosphorylation of TCR-zeta, CD3 epsilon, or ZAP-70 [54].
• We show that anti-CD3 antibodies induce activation of fetal thymocytes as early as day 13 of fetal thymus development, 2 days before CD3 can be detected by flow cytometry [55].
• To examine which cell surface molecules can operate as transducers of activation signals to early fetal thymocytes, we analyzed the ability of mAb to CD3 and Thy-1 to induce fetal thymocyte activation [55].
• Although CD3epsilon could be produced at high yield when directed to inclusion bodies, the refolded monomeric CD3epsilon was not native as judged by monoclonal antibody binding using surface plasmon resonance and was largely unstructured by (15)N-(1)H two-dimensional NMR analysis [5].
• In immunofluorescence, antigen-dependent synapses show multiple patches of CD3 and LFA-1 with a variable overlap [56].

References