Affinage

CD3D

T-cell surface glycoprotein CD3 delta chain · UniProt P04234

Length
171 aa
Mass
18.9 kDa
Annotated
2026-06-09
71 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CD3δ (CD3D) is an invariant transmembrane subunit of the T-cell receptor (TCR)/CD3 complex that links antigen receptor assembly to T-cell development and signaling (PMID:7719941, PMID:9135151). It associates with CD3ε to form a CD3δε dimer that constitutes one of two mutually exclusive complexes (the other being CD3γε), generating distinct αβδε and αβγε receptor forms rather than a single combined complex, with exactly one copy of CD3δ per surface receptor (PMID:1826255, PMID:15459203). During ordered ER assembly, CD3δε is the first partner for nascent TCRα, forming an αδε trimer in the rate-limiting step that protects TCRα from accelerated degradation; unassembled CD3δ is recognized by calnexin via incompletely trimmed N-glycans and is otherwise degraded near the ER and in lysosomes to prevent surface display of lone subunits (PMID:7719941, PMID:8621641, PMID:2150597). CD3δ is essential for surface expression of αβ TCR and for coupling receptor engagement to downstream signaling, and its loss arrests development specifically at the CD4+CD8+ double-positive stage of the αβ lineage while sparing pre-TCR-mediated DN→DP transition (PMID:9135151, PMID:1530953, PMID:34249896). CD3δ couples TCR engagement to ERK MAP kinase activation and thymocyte positive selection through its extracellular/transmembrane domains, correlating with LAT and CD3ζ phosphorylation in lipid rafts and with selective association with the raft-localized CD8αβ co-receptor (PMID:10935641, PMID:12215456). Its cytoplasmic domain is dispensable for assembly and signaling but is required for ligand-induced (not antigen-induced) TCR down-modulation (PMID:1530953, PMID:9126976, PMID:10545476). CD3γ and CD3δ have partially overlapping roles, and a species difference in γδ TCR composition—human γδ receptors incorporate CD3δ whereas mouse γδ receptors do not—explains divergent immunodeficiency phenotypes (PMID:9763617, PMID:17923503). Loss-of-function in CD3D causes a severe combined immunodeficiency that is correctable in patient hematopoietic stem/progenitor cells by adenine base editing, restoring mature T-cell production with diverse TCR repertoires (PMID:36944331).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1988 Medium

    Establishing how CD3δ achieves T cell-restricted expression located the regulatory logic of the gene before its protein assembly was understood.

    Evidence DNase I hypersensitivity mapping and reporter transfection in T and non-T cell lines

    PMID:2847918

    Open questions at the time
    • Promoter itself not T cell-restricted; element-level dissection deferred
    • Trans-acting factors not identified in this study
  2. 1990 Medium

    Dissection of the 3' enhancer (δA/δB) and identification of the ER/lysosomal degradation of unassembled CD3δ defined both transcriptional control and the quality-control fate of orphan subunits.

    Evidence Enhancer deletion/footprinting reporter assays; metabolic pulse-chase in transfected fibroblasts and Lec1 cells with lysosomotropic/temperature-block treatments

    PMID:2136828 PMID:2150597

    Open questions at the time
    • Protease responsible for ER degradation not identified
    • Enhancer factors named only by binding-site conservation
  3. 1991 High

    Reciprocal co-IP showed CD3δ and CD3γ form mutually exclusive complexes with CD3ε, resolving whether the receptor contains one or two CD3 dimer types, and revealed that anti-CD3 antibody epitopes are conformational composites formed upon dimerization.

    Evidence Co-immunoprecipitation and competition assays in transfected COS cells; immunofluorescence and IP across multiple antibody clones

    PMID:1717585 PMID:1826255

    Open questions at the time
    • Stoichiometry per surface complex not quantified here
    • Functional consequences of the two complex forms unaddressed
  4. 1992 High

    Functional reconstitution established that CD3δ is required for αβ TCR surface expression and effector function while its cytoplasmic domain is dispensable, and that most CD3δ is physically linked to CD4/CD8 co-receptors on resting cells.

    Evidence CTL clone with CD3δ mRNA loss reconstituted with native or tail-less CD3δ; co-IP with anti-CD4/CD8 plus 2D-PAGE and peptide mapping in primary T cells

    PMID:1396954 PMID:1530953

    Open questions at the time
    • Domain mediating co-receptor linkage not mapped at this stage
    • Mechanism of CD3δ-dependent surface expression not yet biochemical
  5. 1994 Medium

    Identifying Raf kinase as a partner of hypophosphorylated CD3γ/CD3δ proposed a direct biochemical link between the receptor and a serine/threonine kinase cascade.

    Evidence Co-immunoprecipitation from murine T cells with COS-cell subunit specificity mapping

    PMID:8132616

    Open questions at the time
    • Single lab, not reciprocally validated
    • Physiological role of the Raf–CD3δ association not established
  6. 1995 High

    Pulse-chase assembly kinetics defined the ordered ER pathway, placing TCRα–CD3δε as the rate-limiting first step that protects nascent TCRα from degradation.

    Evidence Metabolic pulse-chase and IP of assembly intermediates in primary murine thymocytes and T cells

    PMID:7719941

    Open questions at the time
    • Chaperone machinery driving the step not fully defined here
    • Quantitative kinetics in human cells not addressed
  7. 1996 High

    Demonstrating calnexin association specifically with monomeric CD3δ and TCRα bearing monoglucosylated glycans linked glycan-dependent ER quality control to TCR subunit assembly.

    Evidence Metabolic labeling, co-IP, and glycan analysis in murine splenic T cells

    PMID:8621641

    Open questions at the time
    • Glucose trimming required for calnexin binding to TCRα but not CD3δ — basis of differential dependence unresolved
  8. 1997 High

    CD3δ knockout mice and pre-TCR biochemistry separated CD3δ's roles: it is physically present in the pre-TCR but functionally required only for the αβ DP→SP transition (selection), not for DN→DP, and its cytoplasmic motifs govern ligand-induced down-modulation.

    Evidence CD3δ−/− mice with thymic flow cytometry; surface IP of biotinylated thymocytes; CTL clones with truncated CD3δ/γ and FACS

    PMID:9126976 PMID:9135151 PMID:9348303

    Open questions at the time
    • Mechanism coupling CD3δ to selection not yet defined (addressed later)
    • Down-modulation findings single-lab/Medium confidence
  9. 1998 High

    Double-knockout epistasis and biochemical heterogeneity studies showed CD3γ and CD3δ have partially overlapping essential functions and that CD3δ exists as monomeric and oligomeric species with thymocyte-specific glycan handling.

    Evidence CD3γδ−/− double-knockout mice with thymic flow cytometry; non-reducing/reducing 2D-PAGE and co-IP in thymocytes vs. splenic T cells

    PMID:9603915 PMID:9763617

    Open questions at the time
    • Molecular basis of functional redundancy not resolved
    • Significance of CD3δ oligomers uncharacterized
  10. 2000 High

    Mapping the selection defect to ERK activation showed CD3δ couples TCR engagement to a specific MAP kinase pathway and raft-associated phosphorylation, with the requirement residing in its extracellular/transmembrane domains.

    Evidence Kinase assays (ERK/JNK/p38), phosphotyrosine immunoblotting of lipid raft fractions, and tail-less CD3δ transgenic rescue in CD3δ−/− mice

    PMID:10935641

    Open questions at the time
    • Precise structural feature transmitting the signal not identified
    • How ERK selectivity arises mechanistically unresolved
  11. 2001 Medium

    Comparing CD3δ association with αβ versus γδ TCR showed weaker incorporation into γδ complexes attributable to the TCRγ chain rather than the cellular environment.

    Evidence Metabolic labeling and IP in αβ and γδ T lymphoma lines and TCRγδ transfectants

    PMID:11439162

    Open questions at the time
    • Single lab
    • Structural basis of weaker TCRγ association not defined
  12. 2002 Medium

    Linking CD3δ to selective CD8αβ (not CD8αα) association and characterizing the CD3δ promoter elements connected the receptor to raft-localized co-receptor function and detailed its transcriptional control.

    Evidence Anti-CD8 co-IP and calcium flux in hybridomas/transgenic mice; transgenic mice and mutant reporter scanning for promoter elements

    PMID:12215456 PMID:12324448

    Open questions at the time
    • Direct contact interface between CD3δ and CD8αβ not mapped
    • Promoter element functions characterized largely in single lab
  13. 2004 High

    Quantitative 2D-PAGE established that the surface receptor contains exactly one CD3δ and one CD3γ, fixing the stoichiometry of the complex.

    Evidence Surface biotinylation and 2D nonreducing/reducing SDS-PAGE of thymocytes from tagged transgenic/knockout mice

    PMID:15459203

    Open questions at the time
    • Stoichiometry of cytoplasmic/intracellular assembly intermediates not addressed
  14. 2006 Medium

    Cross-species transgenic rescue showed human CD3δε can substitute for mouse CD3γ in pre-TCR signaling and DN→DP progression, but with attenuated downstream signaling and selection.

    Evidence Human CD3δε / CD3δ transgenes in CD3γ−/− and CD3γδ−/− mice with thymic flow cytometry and signaling assays

    PMID:16412509 PMID:16888097

    Open questions at the time
    • Single-lab rescue experiments
    • Structural instability inferred, not directly visualized
  15. 2007 High

    Defining the species difference in γδ TCR composition (human γδ incorporates CD3δ, mouse does not) explained why CD3γ deficiency spares γδ T cells in humans but not mice.

    Evidence Blue native PAGE stoichiometry and human CD3δ transgene rescue in CD3γδ-double-deficient mice

    PMID:17923503

    Open questions at the time
    • Structural basis of differential CD3δ incorporation in γδ receptors not resolved
  16. 2021 Medium

    Stable CD3D knockdown in human Jurkat cells confirmed its requirement for TCR ER export and ζζ dimer formation, while showing immature progenitors tolerate loss with residual surface expression.

    Evidence Stable shRNA knockdown in Jurkat cells and mouse fetal thymus organ culture with flow cytometry and IP

    PMID:34249896

    Open questions at the time
    • Single lab
    • Survival-signaling role of residual receptor in progenitors not directly demonstrated
  17. 2023 High

    Adenine base editing of patient HSPCs corrected a pathogenic CD3D mutation and restored functional T-cell production, providing direct evidence that CD3D loss-of-function causes a correctable T-cell immunodeficiency.

    Evidence ABE of patient HSPCs, artificial thymic organoid differentiation, TCR repertoire sequencing, and immunodeficient mouse engraftment

    PMID:36944331

    Open questions at the time
    • Long-term durability and off-target profile not detailed here
  18. 2025 Low

    A report of TRIM13-mediated CD3D ubiquitination in cardiomyocytes proposes a degradation partner outside the canonical T-cell context.

    Evidence Co-IP and ubiquitination assay with TRIM13 knockdown in an OGD cardiomyocyte/myocardial infarction model

    PMID:40746991

    Open questions at the time
    • Single Co-IP without reciprocal validation
    • CD3D role in cardiomyocytes is atypical and not independently confirmed
    • Relevance to T-cell biology unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CD3δ's extracellular/transmembrane domains structurally transmit the ERK-selective signal that drives positive selection, and the precise molecular interface with CD8αβ, remain undefined.
  • No atomic-resolution structure of the signaling-competent CD3δ interface in the corpus
  • Mechanism of ERK pathway selectivity unresolved
  • CD3δ–CD8αβ contact residues unmapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 2 GO:0060089 molecular transducer activity 2 GO:0060090 molecular adaptor activity 2
Localization
GO:0005783 endoplasmic reticulum 3 GO:0005886 plasma membrane 3
Pathway
R-HSA-168256 Immune System 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-1266738 Developmental Biology 2 R-HSA-162582 Signal Transduction 2
Partners
CANX (CALNEXIN)CD3ECD8ACD8BRAF1TRA (TCRΑ)TRIM13
Complex memberships
CD3δε dimerTCR/CD3 complexpre-TCR complex

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 CD3δ and CD3γ form mutually exclusive complexes with CD3ε, producing two distinct TCR/CD3 complex forms (αβγε and αβδε) rather than a single αβγδε complex, as demonstrated by reciprocal co-immunoprecipitation and competition for CD3ε binding in transfected COS cells. Co-immunoprecipitation, COS cell transfection competition assay The EMBO journal High 1826255
1991 A conformational epitope on CD3ε is exposed only upon association with either CD3δ or CD3γ, and this composite epitope is the main target of widely used anti-CD3 monoclonal antibodies (OKT3, UCHT1, Leu-4, WT31), as shown by immunofluorescence and immunoprecipitation in COS cells singly or doubly transfected with CD3 subunit genes. Immunofluorescence of transfected COS cells, immunoprecipitation Journal of immunology High 1717585
1995 TCR assembly proceeds through initial association of TCRα with CD3δε to form an αδε trimer, and TCRβ with CD3γε to form a βγε trimer; these trimers then associate and αβ disulfide bond formation occurs. The rate-limiting step in CD4+CD8+ thymocytes is the initial TCRα–CD3δε association, which protects nascent TCRα from accelerated ER degradation. Metabolic pulse-chase, immunoprecipitation in primary murine thymocytes and T cells Immunity High 7719941
1996 Calnexin associates exclusively with unassembled, monomeric CD3δ and TCRα glycoproteins bearing incompletely trimmed (monoglucosylated) N-glycans in the ER, prior to their incorporation into multisubunit TCR complexes; glucose trimming is required for efficient calnexin association with TCRα but not CD3δ. Metabolic labeling, co-immunoprecipitation, glycan analysis in murine splenic T cells The Journal of biological chemistry High 8621641
1997 CD3δ is required for the transition of CD4+CD8+ double-positive thymocytes to single-positive stages (positive/negative selection) but is dispensable for pre-TCR-mediated CD4−CD8− to CD4+CD8+ transition, as shown by CD3δ-knockout mice which arrest development specifically at the DP stage of αβ T cell lineage while γδ T cell development is unaffected. Gene knockout (CD3δ−/− mice), flow cytometry of thymic subpopulations The EMBO journal High 9135151
1992 CD3δ chain is essential for surface expression of TCRαβ; loss of CD3δ mRNA results in TCR/CD3 complexes devoid of TCRαβ at the cell surface and loss of activation for cytolysis and IFN-γ production. Transfection with cytoplasmic domain-deleted CD3δ fully restores surface expression and effector functions, indicating the CD3δ cytoplasmic domain is not required for complex assembly or signal transduction. CTL clone with CD3δ mRNA loss, transfection with native or cytoplasmic-deleted CD3δ, functional assays (cytolysis, IFN-γ production) Journal of immunology High 1530953
1992 The majority of CD3δ chains (>90% by densitometry) are physically associated with CD4 or CD8 accessory molecules on resting, non-activated T cells, as demonstrated by co-immunoprecipitation followed by 2D gel electrophoresis and peptide mapping. Co-immunoprecipitation with anti-CD4/anti-CD8, 2D SDS-PAGE, peptide mapping of freshly isolated splenic T cells European journal of immunology High 1396954
1997 CD3δ is physically associated with pre-TCR complexes in primary thymocytes (pTα–TCRβ–CD3γ–CD3δ–CD3ε–ζ), but CD3δ is not functionally required for the pre-TCR-mediated DN→DP transition, as CD3δ−/− mice generate normal numbers of DP thymocytes. Surface immunoprecipitation of biotinylated primary thymocytes, CD3δ−/− mouse analysis The Journal of experimental medicine High 9348303
2000 CD3δ couples TCR engagement to ERK MAP kinase activation and thymocyte positive selection; CD3δ−/− thymocytes show selective deficiency in ERK activation but not other MAP kinases, correlating with impaired tyrosine phosphorylation of LAT and of CD3ζ in lipid rafts. Expression of tail-less CD3δ rescues both ERK activation and positive selection, mapping the requirement to the extracellular and/or transmembrane domains. Kinase activity assays (ERK, JNK, p38), phosphotyrosine immunoblotting of lipid raft fractions, CD3δ−/− mice with transgenic rescue Nature High 10935641
2002 CD3δ selectively co-immunoprecipitates with CD8αβ (but not CD8αα), linking the TCR·CD3 complex to raft-associated CD8αβ; this association is absent in CD3δ-null TCR variants and promotes TCR aggregate formation and calcium mobilization upon cross-linking. Co-immunoprecipitation with anti-CD8 in T cell hybridomas and transgenic mice, calcium flux assay The Journal of biological chemistry High 12215456
1990 Unassembled CD3δ subunits are degraded in or near the ER by a protease-sensitive mechanism not requiring Golgi transport, with a secondary checkpoint delivering ~25% of unassembled CD3δ to lysosomes for degradation, preventing surface expression of single subunits. Metabolic pulse-chase in transfected fibroblasts and CHO Lec1 cells, lysosomotropic agent treatment, temperature-block experiments International immunology High 2150597
1994 Raf serine/threonine kinase is associated with the TCR/CD3 complex in unstimulated murine T cells, and specifically binds to a hypophosphorylated form of CD3γ and CD3δ but not CD3ε or CD3ζ chains in COS cell expression system. Co-immunoprecipitation from murine T cells, COS cell transfection with individual CD3 chains The Journal of biological chemistry Medium 8132616
1997 The CD3δ cytoplasmic domain (containing dileucine and tyrosine motifs) is required for CD3 ligand-induced TCR/CD3 down-modulation; a CTL clone expressing cytoplasmically truncated CD3δ and CD3γ is defective in ligand-induced and PMA-induced down-modulation but retains antigen-specific cytolysis and IFN-γ gene expression. CTL clone reconstitution with truncated CD3 chains, FACS analysis of TCR/CD3 surface levels, PKC inhibitor studies Journal of immunology Medium 9126976
1998 CD3γ and CD3δ play essential, partially overlapping roles in both αβ and γδ T cell development: double-knockout (CD3γδ−/−) mice show complete arrest of thymocyte development at the DN stage and absence of both αβ and γδ T cells, whereas single knockouts each retain some T cell development. Double gene knockout mice (CD3γδ−/−), flow cytometry of thymic subpopulations The Journal of experimental medicine High 9763617
2004 The surface TCR/CD3 complex contains exactly one molecule each of CD3δ and CD3γ, as determined by two-dimensional nonreducing/reducing gel electrophoresis of surface-biotinylated thymocytes from mice expressing tagged transgenic CD3 chains on knockout backgrounds. Surface biotinylation, 2D nonreducing/reducing SDS-PAGE of thymocytes from transgenic/knockout mice The Journal of biological chemistry High 15459203
2007 Human γδ TCR incorporates CD3δ with stoichiometry TCRγδ·CD3ε₂δγζ₂, whereas mouse γδ TCR does not incorporate CD3δ and has stoichiometry TCRγδ·CD3ε₂γ₂ζ₂; this structural difference explains why CD3γ-deficient humans retain γδ T cells (CD3δ substitutes) while CD3γ-deficient mice lose γδ T cells. Blue native PAGE, anti-TCR antibodies, human CD3δ transgene rescue in CD3γδ-double-deficient mice The Journal of experimental medicine High 17923503
1999 Antigen-induced TCR/CD3 down-modulation does not require CD3δ or CD3γ cytoplasmic domains (in contrast to anti-CD3 mAb-induced down-modulation which does require these domains); antigen-induced internalization of TCRβ was confirmed by confocal microscopy in CTL clones with truncated CD3δ/γ chains. CTL clones with cytoplasmic-deleted CD3δ and CD3γ, confocal microscopy, PTK inhibitor PP1, FACS International immunology Medium 10545476
1998 CD3δ proteins exist as both monomeric and disulfide-linked oligomeric species in murine T cells; in CD4+CD8+ thymocytes (unlike splenic T cells), glucose residues are not invariably removed from CD3δ before CD3ε association; calnexin associates with both monomeric and disulfide-linked CD3δ species. Metabolic labeling, non-reducing/reducing 2D-PAGE, co-immunoprecipitation in thymocytes and splenic T cells The Journal of biological chemistry Medium 9603915
2001 CD3δ chains associate less strongly with TCRγδ heterodimers than with TCRαβ heterodimers, with the impaired reactivity attributable specifically to weaker association with TCRγ chains rather than to differences in the intracellular environment of γδ vs. αβ T cells. Metabolic labeling, immunoprecipitation in αβ and γδ T lymphoma cell lines and TCRγδ transfectants Scandinavian journal of immunology Medium 11439162
2006 Human CD3δ/ε heterodimer can functionally substitute for mouse CD3γ/ε in supporting pre-TCR-mediated DN→DP transition, as shown by a human CD3δε transgene rescuing the pre-TCR defect in CD3γ-deficient and CD3γδ-double-deficient mice. Human CD3δε transgene in CD3γ−/− and CD3γδ−/− mice, thymic subset analysis by flow cytometry Molecular immunology Medium 16412509
2006 Human CD3δ can substitute for mouse CD3γ in pre-TCR-mediated DN→DP progression when expressed as a transgene in CD3γδ-double-deficient mice, but leads to attenuated TCR signaling and less efficient positive/negative selection compared to wild-type, correlating with structural instability of TCR complexes. Human CD3δ transgene in CD3δ/γ double-deficient mice, flow cytometry, TCR signaling assays Blood Medium 16888097
2021 Stable knockdown of CD3D in mature Jurkat T cells causes strong ER retention of TCR complexes, loss of ζζ dimers, and failure to reach the cell surface (<11% of controls); immature T-cell progenitors show greater plasticity, allowing some TCR surface expression that may support survival signaling. Stable shRNA knockdown in Jurkat T cells, mouse fetal thymus organ culture, flow cytometry, immunoprecipitation Frontiers in cell and developmental biology Medium 34249896
1988 A 400 bp T cell-specific transcriptional enhancer located 0.6 kb downstream of the polyadenylation site of the CD3δ gene drives T cell-restricted expression in a position- and orientation-independent manner; the promoter itself is not T cell-restricted. DNase I hypersensitivity mapping, reporter transfection assays in T and non-T cell lines The EMBO journal Medium 2847918
1990 Two cis-acting elements in the CD3δ 3' enhancer (δA and δB) mediate T cell-specific expression: δA acts as an independent enhancer bound by T cell-specific nuclear factors, while δB has no independent function but augments δA activity; protein-binding sites are conserved across other TCR/CD3 genes. Deletion analysis of enhancer fragments, reporter transfection, DNase I footprinting/gel shift The EMBO journal Medium 2136828
2002 The murine CD3δ promoter directs T cell-preferred expression via four positive regulatory elements (two initiator-like sites recruiting TFII-I, one Ets binding site, one CREB site) and one negative element using YY1; NERF-2, Elf-1, and Ets-1 contribute to lymphocyte-specific expression. Transgenic mice, deletion/substitution mutant reporter transfections, transcription factor binding studies The Journal of biological chemistry Medium 12324448
2023 A pathogenic mutation in CD3D can be corrected in patient hematopoietic stem and progenitor cells by adenine base editing (ABE), yielding 71.2% correction efficiency; edited HSPCs differentiated in artificial thymic organoids to produce mature T cells with diverse TCR repertoires and TCR-dependent effector functions. Adenine base editing of patient HSPCs, artificial thymic organoid differentiation, TCR repertoire sequencing, immunodeficient mouse transplantation Cell High 36944331
2025 TRIM13 ubiquitin ligase interacts with CD3D protein and promotes its ubiquitination; knockdown of TRIM13 increases CD3D ubiquitination and decreases CD3D levels, thereby alleviating OGD-induced cardiomyocyte apoptosis in a myocardial infarction context. Co-immunoprecipitation, ubiquitination assay, in vitro and in vivo knockdown, OGD cardiomyocyte model iScience Low 40746991

Source papers

Stage 0 corpus · 71 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 CD3 delta deficiency arrests development of the alpha beta but not the gamma delta T cell lineage. The EMBO journal 167 9135151
1991 The CD3-gamma and CD3-delta subunits of the T cell antigen receptor can be expressed within distinct functional TCR/CD3 complexes. The EMBO journal 108 1826255
2000 CD3delta couples T-cell receptor signalling to ERK activation and thymocyte positive selection. Nature 107 10935641
1991 A conformational epitope expressed upon association of CD3-epsilon with either CD3-delta or CD3-gamma is the main target for recognition by anti-CD3 monoclonal antibodies. Journal of immunology (Baltimore, Md. : 1950) 82 1717585
1988 A T cell-specific enhancer is located in a DNase I-hypersensitive area at the 3' end of the CD3-delta gene. The EMBO journal 77 2847918
2002 CD3 delta establishes a functional link between the T cell receptor and CD8. The Journal of biological chemistry 75 12215456
1995 TCR alpha-CD3 delta epsilon association is the initial step in alpha beta dimer formation in murine T cells and is limiting in immature CD4+ CD8+ thymocytes. Immunity 65 7719941
1992 Role of CD3 delta in surface expression of the TCR/CD3 complex and in activation for killing analyzed with a CD3 delta-negative cytotoxic T lymphocyte variant. Journal of immunology (Baltimore, Md. : 1950) 64 1530953
2007 Different composition of the human and the mouse gammadelta T cell receptor explains different phenotypes of CD3gamma and CD3delta immunodeficiencies. The Journal of experimental medicine 63 17923503
2017 Improved Brain Insulin/IGF Signaling and Reduced Neuroinflammation with T3D-959 in an Experimental Model of Sporadic Alzheimer's Disease. Journal of Alzheimer's disease : JAD 62 27802237
1997 Subunit composition of pre-T cell receptor complexes expressed by primary thymocytes: CD3 delta is physically associated but not functionally required. The Journal of experimental medicine 62 9348303
2023 Human T cell generation is restored in CD3δ severe combined immunodeficiency through adenine base editing. Cell 60 36944331
2020 Concomitant overexpression of mir-182-5p and mir-182-3p raises the possibility of IL-17-producing Treg formation in breast cancer by targeting CD3d, ITK, FOXO1, and NFATs: A meta-analysis and experimental study. Cancer science 52 33283362
2016 T3D-959: A Multi-Faceted Disease Remedial Drug Candidate for the Treatment of Alzheimer's Disease. Journal of Alzheimer's disease : JAD 52 26836193
2012 Isolation of reovirus T3D mutants capable of infecting human tumor cells independent of junction adhesion molecule-A. PloS one 50 23110175
2011 A leaky mutation in CD3D differentially affects αβ and γδ T cells and leads to a Tαβ-Tγδ+B+NK+ human SCID. The Journal of clinical investigation 46 21926461
2005 Sensitization to apoptosis underlies KrasD12-dependent oncolysis of murine C26 colorectal carcinoma cells by reovirus T3D. Journal of virology 46 16282499
2020 An Exploratory Phase IIa Study of the PPAR delta/gamma Agonist T3D-959 Assessing Metabolic and Cognitive Function in Subjects with Mild to Moderate Alzheimer's Disease. Journal of Alzheimer's disease : JAD 45 31884472
1996 Calnexin associates exclusively with individual CD3 delta and T cell antigen receptor (TCR) alpha proteins containing incompletely trimmed glycans that are not assembled into multisubunit TCR complexes. The Journal of biological chemistry 43 8621641
2020 CD3D is associated with immune checkpoints and predicts favorable clinical outcome in colon cancer. Immunotherapy 41 31914842
2016 Targeting Alzheimer's Disease Neuro-Metabolic Dysfunction with a Small Molecule Nuclear Receptor Agonist (T3D-959) Reverses Disease Pathologies. Journal of Alzheimer's disease & Parkinsonism 40 27525190
1992 Immunoglobulin heavy-chain and CD3 delta-chain gene enhancers are DNase I-hypersensitive in hemopoietic progenitor cells. Proceedings of the National Academy of Sciences of the United States of America 39 1533043
1992 Biochemical evidence of the physical association of the majority of CD3 delta chains with the accessory/co-receptor molecules CD4 and CD8 on nonactivated T lymphocytes. European journal of immunology 37 1396954
1990 Tissue-specific nuclear factors mediate expression of the CD3 delta gene during T cell development. The EMBO journal 37 2136828
2008 A strategy for genetic modification of the spike-encoding segment of human reovirus T3D for reovirus targeting. Gene therapy 32 18650851
2008 Transient infection of freshly isolated human colorectal tumor cells by reovirus T3D intermediate subviral particles. Cancer gene therapy 31 18259212
2019 High CD3D/CD4 ratio predicts better survival in muscle-invasive bladder cancer. Cancer management and research 30 31114346
2002 T cell-specific expression of the murine CD3delta promoter. The Journal of biological chemistry 26 12324448
1997 Role of CD3gamma and CD3delta cytoplasmic domains in cytolytic T lymphocyte functions and TCR/CD3 down-modulation. Journal of immunology (Baltimore, Md. : 1950) 26 9126976
1998 Essential and partially overlapping role of CD3gamma and CD3delta for development of alphabeta and gammadelta T lymphocytes. The Journal of experimental medicine 22 9763617
2021 CD3D, GZMK, and KLRB1 Are Potential Markers for Early Diagnosis of Rheumatoid Arthritis, Especially in Anti-Citrullinated Protein Antibody-Negative Patients. Frontiers in pharmacology 21 34603038
2019 Kinetics of Oncolytic Reovirus T3D Replication and Growth Pattern in Mesenchymal Stem Cells. Cell journal 20 31863653
2014 Mammalian orthoreovirus T3D infects U-118 MG cell spheroids independent of junction adhesion molecule-A. Gene therapy 20 24739522
2021 CD3G or CD3D Knockdown in Mature, but Not Immature, T Lymphocytes Similarly Cripples the Human TCRαβ Complex. Frontiers in cell and developmental biology 18 34249896
1990 Recognition for degradation in the endoplasmic reticulum and lysosomes prevents the transport of single TCR beta and CD3 delta subunits of the T-cell antigen receptor to the surface of cells. International immunology 18 2150597
2004 CD3 delta immunodeficiency. Current opinion in allergy and clinical immunology 17 15640687
2011 Hematopoietic stem cell transplantation for CD3δ deficiency. The Journal of allergy and clinical immunology 16 21757226
1994 CD3 delta enhancer. CREB interferes with the function of a murine CD3-delta A binding factor (M delta AF). Journal of immunology (Baltimore, Md. : 1950) 16 8144959
2006 Overlapping functions of human CD3delta and mouse CD3gamma in alphabeta T-cell development revealed in a humanized CD3gamma-mouse. Blood 13 16888097
2001 On the role of CD3delta chains in TCRgammadelta/CD3 complexes during assembly and membrane expression. Scandinavian journal of immunology 13 11439162
1999 Antigen-induced TCR-CD3 down-modulation does not require CD3delta or CD3gamma cytoplasmic domains, necessary in response to anti-CD3 antibody. International immunology 13 10545476
2005 Severe combined immunodeficiency caused by a splicing abnormality of the CD3delta gene. European journal of pediatrics 11 15729559
1996 CD3 gamma, CD3 delta, and CD3 zeta mRNA in adult human marrow hematopoietic progenitors correlates with surface CD2 and CD7 expression. Experimental hematology 11 8913286
2013 Human CD3γ, but not CD3δ, haploinsufficiency differentially impairs γδ versus αβ surface TCR expression. BMC immunology 10 23336327
1994 Association of Raf with the CD3 delta and gamma chains of the T cell receptor-CD3 complex. The Journal of biological chemistry 10 8132616
1989 The CD3 delta gene encodes multiple transcripts regulated by transcriptional and post-transcriptional mechanisms. European journal of immunology 10 2532602
2000 Protection of CD3 delta knockout mice from lymphocytic choriomeningitis virus-induced immunopathology: implications for viral neuroinvasion. Virology 9 10753703
2023 CD3D and CD247 are the molecular targets of septic shock. Medicine 8 37478215
2015 Comparative proteomic analyses demonstrate enhanced interferon and STAT-1 activation in reovirus T3D-infected HeLa cells. Frontiers in cellular and infection microbiology 8 25905045
1998 Calnexin associates with monomeric and oligomeric (disulfide-linked) CD3delta proteins in murine T lymphocytes. The Journal of biological chemistry 8 9603915
1998 Altered functional responsiveness of thymocyte subsets from CD3delta-deficient mice to TCR-CD3 engagement. International immunology 8 9796915
2012 Non-Biased Enrichment Does Not Improve Quantitative Proteomic Delineation of Reovirus T3D-Infected HeLa Cell Protein Alterations. Frontiers in microbiology 7 23024642
2006 Different role for mouse and human CD3delta/epsilon heterodimer in preT cell receptor (preTCR) function: human CD3delta/epsilon heterodimer restores the defective preTCR function in CD3gamma- and CD3gammadelta-deficient mice. Molecular immunology 7 16412509
2004 Biochemical evidence for the presence of a single CD3delta and CD3gamma chain in the surface T cell receptor/CD3 complex. The Journal of biological chemistry 7 15459203
1993 Induction of CD3 delta epsilon omega by phorbol 12-myristate 13-acetate. European journal of immunology 7 8500530
2023 Hypomethylation of CD3D promoter induces immune cell infiltration and supports malignant phenotypes in uveal melanoma. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 6 37651092
2016 CD3D and PRKCQ work together to discriminate between B-cell and T-cell acute lymphoblastic leukemia. Computers in biology and medicine 6 27494091
2007 New alleles of chicken CD8 alpha and CD3d found in Chinese native and western breeds. Veterinary immunology and immunopathology 6 17904644
1991 Cloning of a novel cell type from human fetal liver expressing cytoplasmic CD3 delta and epsilon but not membrane CD3. International immunology 6 1831653
1990 Non-HLA genetic factors and insulin dependent diabetes mellitus in the Japanese: TCRA, TCRB and TCRG, INS, THY1, CD3D and ETS1. Disease markers 6 1982251
2015 Comparative proteomic analyses of two reovirus T3D subtypes and comparison to T1L identifies multiple novel proteins in key cellular pathogenic pathways. Proteomics 5 25900405
2013 HeLa cell response proteome alterations induced by mammalian reovirus T3D infection. Virology journal 5 23799967
2010 Polymorphisms of the T cell receptor CD3delta and CD3epsilon chains affect anti-CD3 antibody binding and T cell activation. Molecular immunology 5 20638133
1999 Molecular mechanisms in the TCR (TCR alpha beta-CD3 delta epsilon, gamma epsilon) interaction with zeta 2 homodimers: clues from a 'phenotypic revertant' clone. International immunology 5 10383932
1993 Translocation of CD3D gene in an acute myeloid leukemia (M5) with t(11;17)(q23;21). Cancer genetics and cytogenetics 5 8281523
2024 CD3D silencing alleviates diabetic nephropathy via inhibition of JAK/STAT pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 4 39530557
2026 Exploration of CD2 and CD3D as potential immune-related biomarkers for IORT in breast cancer treatment. Medicine 0 42065189
2025 Variants in Lrrk2 and Snca deficiency do not alter the course of primary encephalitis due to neurotropic reovirus T3D in newborn mice. PloS one 0 40471880
2025 TRIM13 prevents cardiomyocyte injury by affecting apoptosis through interacting with CD3D in myocardial infarction. iScience 0 40746991
2025 Calcitonin Alleviates Sepsis-Induced Acute Lung Injury by Inhibiting the HMGB1/MyD88/NF-κB Pathway by Targeting CD3D. Frontiers in bioscience (Landmark edition) 0 41198548
2016 [Changes of CD3γ, CD3δ and CD3epsilon chains mRNAs in lead-poisoned patients after chelate treatment]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 0 27053617

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