CD3 Antibody Review





  • CD3 antigen is a surface structure associated with the T-cell receptor (TCR) to form a complex involved in antigen recognition and signal transduction. PMID: 15885124

  • a crucial molecule in T cell signal transduction. PMID: 15046399

  • The TCR-CD3 complex consists of the clonotypic disulfide-linked TCRalphabeta or TCRdeltagamma heterodimers, and the invariant CD3delta, epsilon, gamma and zeta chains. PMID: 11934875

  • The CD3 complex is present in both alpha/beta and gamma/delta cells and includes at least five proteins (designated gamma, delta, epsilon, zeta and eta). PMID: 1371241

  • T-cell antigen receptor (TCR) heterodimers of both the alpha beta and gamma delta types are expressed at the surface of T cells only in association with a complex of invariant chains called CD3. PMID: 1835791

Normal Expression

  • CD3 antigen, formerly thought to be specific for T lymphocytes, has been identified in Purkinje cells of the cerebellum and gastric parietal cells in several species, including humans. PMID: 16308105

  • human gammadelta T cells constitutively express approximately twofold more of the TCR/CD3 complex than alphabeta T cells. PMID: 11237559

  • Although membranous CD3 and FcgammaRIIB are crucial regulators on different cells in the immune system, both CD3epsilon and FcgammaRIIB are expressed on Purkinje cells in the cerebellum. PMID: 17502348

  • CD3 epsilon antigen expression in cytoplasm and cell membranes of gastric parietal cells was graded subjectively based on the number of positive cells. CD3 epsilon antigen was found on gastric parietal cells in all but one species studied, with varying expression in membranes and cytoplasm. PMID: 12812314

  • Recently, we found CD3-CD4(bright) cells with comparative specificity for normal rat liver. PMID: 12191006

  • In tonsil control sections, CD3-epsilon and CD3-zeta were always co-expressed in almost equal numbers. PMID: 10098746

  • The TCR-associated CD3 complex consists of four subunits, i.e. CD3 gamma, delta, epsilon and zeta, which are expressed very early in T cell development prior to the expression of the TCR and the pre-TCR alpha chain. PMID: 9885898

  • In this paper we have shown that unlike adult peripheral blood NK cells these uterine NK cells express cytoplasmic CD3 and CD3 zeta, but CD3 gamma and CD3 delta were not found in the majority of cells. PMID: 9606993

  • the quantitative analysis of CD3 and CD7 and their combined evaluation may enable a distinction between normal and leukaemic T cells and could facilitate the monitoring of minimal residual disease. PMID: 8703826

  • the human parathyroid cells express a CD3-like molecule with the ability to interact in PTH release. PMID: 7491523

  • Cytoplasmic expression of the leu-4 (CD3) antigen in developing Purkinje cells in the rat cerebellum. PMID: 8232751

  • We demonstrate that adult peripheral blood NK cell lines and clones express cytoplasmic CD3 epsilon proteins, but not CD3 delta or gamma. CD3 epsilon proteins were detected by immunoprecipitation, Western blot analysis, and immunofluorescence using antiserum directed against the cytoplasmic domain of CD3 epsilon. Although resting, adult peripheral blood NK cells have essentially undetectable levels of CD3 epsilon protein, expression was increased substantially after activation. PMID: 1387664

  • In all hybrid organs the lymphocytes in the T cell regions showed an intense CD3 immune reaction, located particularly in the cytoplasmic membrane and at the cytoplasmic border. PMID: 1534820

Abnormal Expression

  • HTLV-I infection initiates a process leading to a complete loss of CD3 membrane expression by an epigenetic mechanism which continues along time, despite an early silencing of the viral genome. PMID: 17822534

  • CD3 expression was strong in normal proximal and distal tubular epithelium in most species and in renal oncocytomas, weak in chromophobe carcinoma, and negative in clear cell carcinomas, in papillary renal cell carcinoma, and in a transitional cell carcinoma. PMID: 16308105

  • In the present work we describe a low expression of CD3zeta in synovial fluid (SF) T cells from RA patients compared with peripheral blood (PB) T cells, but no difference in CD3zeta expression between RA and healthy control PB T cells. PMID: 10759780

  • Our results show that high-fat (47 en%) diets suppress expression of CD3 and CD25 antigens. PMID: 10758364

  • For the first time, co-expression of CD79a (JCB117) and CD3 is reported in 10 per cent of cases of T lymphoblastic leukaemia/lymphoma. This finding raises questions about the co-expression of T- and B-cell markers in the development of lymphocytes, benign as well as malignant, and alerts pathologists to a potential problem in diagnosis. PMID: 9924428

  • CD3+ lymphocytes were increased in non-involved skin in moderate and severe psoriasis. PMID: 9298124

  • Adult natural killer (NK) cells had not generally been thought to express CD3 proteins other than zeta; however they were recently demonstrated to express CD3 epsilon in an activated condition. PMID: 7845028

  • Recently, a decreased expression of the signal-transducing CD3 zeta chains has been shown to occur in patients with colorectal or renal-cell carcinoma. PMID: 7989113


  • short-term treatment with an anti-CD3 antibody induces a regulatory T-cell phenotype that restores self-tolerance in a mouse model of atherosclerosis. PMID: 17043169

  • The CD3+CD8+ sub-population is responsible for the increased levels of IL4. PMID: 12952225

  • CD3gamma contributes to, but is not absolutely required for, the regulation of TCR trafficking in resting and Ag-stimulated mature T lymphocytes. PMID: 12794121

  • In adults, the CD3+ CD56+ cell, a cytokine-induced killer (CIK) cell, appears to be a promising effector cell type with the greatest cytotoxicity. PMID: 12627854

  • CD3 gamma contributes essential specialized signaling functions to certain mature T cell responses. PMID: 12407027

  • The mechanism of action of the anti-CD3 monoclonal antibody may involve direct effects on pathogenic T cells, the induction of populations of regulatory cells, or both. PMID: 12037148

  • The nonenzymatic CD3-epsilon protein acted as a potent oncogene when overexpressed early in T lymphocyte development. PMID: 9132282

Diagnostic & Therapeutic Value

  • morphometry of CD3-positive lymphoid cells may add valuable information in the differential diagnosis of mycosis fungoides (MF) and benign dermatoses. PMID: 17496190

  • oral anti-CD3 is effective in the model of STZ-induced diabetes and may be a useful form of therapy for type 1 diabetes in humans. PMID: 17456848

  • Anti-CD3 antibody therapy is a promising clinical approach for the treatment of type 1 diabetes (T1D). PMID: 17130581

  • Parenteral administration of CD3-specific monoclonal antibody is an approved therapy for transplantation in humans and is effective in autoimmune diabetes. PMID: 16715091

  • Although not absolutely specific, a low CD8-CD3 ratio in the epidermal component of a lymphocytic infiltrate supports the diagnosis of mycosis fungoides. PMID: 13679448

  • the bulk culture system of cPBL with rIL-2 and solid phase anti-CD3 antibody may be useful for the development of novel immunotherapy in dogs. PMID: 12679562

  • The decrease in CD3 T cells suggests a connection with the decrease in the host's resistance to infectious diseases. PMID: 12041866

  • CD3 monitoring of antithymocyte globulin therapy in thoracic organ recipients reduced the amount of drug received by each patient, while maintaining CD3 counts less than 100 cells/microl. PMID: 11981432

  • Reduced CD3-zeta expression in tumor-infiltrating lymphocytes (TILs) was strongly correlated with progressive disease in gastric carcinomas. CD3-zeta expression in TILs is considered an immunologic, independent prognostic marker in gastric carcinoma patients. CD3-zeta normalization with cytokine treatment may lead to prolonged survival in advanced gastric carcinoma patients. PMID: 11920499

  • Patients with an unresponsive CD3 receptor as measured by in vitro response to anti-CD3 monoclonal antibodies had a significantly higher incidence of recurrent cancer. PMID: 11895904

  • CD3+CD56+ NK T cells could be actively involved in the development of Th1 mediated autoimmune diseases. PMID: 11882050

  • a decreased CD3-positive T-cell count may be used to predict rapid progression (RP) in HIV-1 infected infants (RR = 2.16, P =.001). PMID: 11496244

  • diminished CD3 expression as shown by flow cytometry may be particularly useful for detecting and enumerating MF/SS cells in hematopoietic tissue of patients with cutaneous T-cell lymphoma. PMID: 10989648

  • In the present study, an anti-CD3 x anti-PSA-BiAb was demonstrated to be effective against prostate carcinoma cells in vitro and in vivo. Therefore this BiAb may be a tool for the immunotherapy of prostate cancer. PMID: 10928069

  • HuM291, a humanized anti-CD3 antibody, may be an immunosuppressive agent associated with less of the acute toxicity and immunogenicity seen with OKT3 therapy. PMID: 10480417, PMID: 10480415

  • prophylactic muromonab CD3-based therapy has a role in patients at high risk of rejection. PMID: 8861551

  • the engineered chimeric anti-CD3 single chain antibody (scUCHT1) may be useful in clinical immunosuppressive treatment. PMID: 8633192

Review Articles

  • CD3-specific antibodies: a portal to the treatment of autoimmunity. PMID: 17641665

  • CD3-specific antibodies as promising tools to aim at immune tolerance in the clinic. PMID: 16818372

  • CD3-specific antibodies restore self-tolerance: mechanisms and clinical applications. PMID: 16214320

  • CD3 delta immunodeficiency. PMID: 15640687

  • Anti-CD3 antibodies: towards clinical antigen-specific immunomodulation. PMID: 15251136



Flow Cytometry (FC)

  • Two-color flow cytometry was then used to quantify the levels of CD3 zeta expression in C1LNL, C2LNL and PBL. PMID: 15274412

  • Flow cytometrical analysis of CD3 zeta on peripheral T lymphocytes from 12 hepatitis C virus (HCV) infected hosts and 36 hepatocellular carcinomas (HCC) bearing patients showed a significantly lower CD3 zeta expression than normal controls. PMID: 14662115

  • Flow cytometric expression of CD3 and CD11b antigens on blood and milk leukocytes, leukocyte differential counts, bacterial counts in milk, and somatic cell counts were determined longitudinally. PMID: 11763169

  • In a prospective clinical study we evaluated subpopulations of lymphocytes and percentage of CD3+/HLA-DR+ lymphocytes using two-color flow cytometry in 40 patients with sepsis and compared them with 34 healthy adults. PMID: 11284925

  • Flow cytometric detection of intracellular myeloperoxidase, CD3 and CD79a. Interaction between monoclonal antibody clones, fluorochromes and sample preparation protocols. PMID: 10986389

  • The expression of CD2 and CD3 was analyzed by flow cytometry, and proliferation of CD2 and CD3 was studied by 3H-thymidine incorporation in phytohaemagglutinin (PHA)- and anti-CD3-stimulated peripheral blood mononuclear cells (PBMC) of 18-month-old children, 25 with and 29 without atopic dermatitis. PMID: 10981527

  • Multicolour flow cytometry was used to analyse pan T-cells (CD3+CD45+CD14-), T-helper-(CD3+CD4+) and T-cytotoxic-(CD3+CD8+) cells. PMID: 10341315

  • Flow cytometric analysis of his lymphocytes revealed a major subpopulation of atypical cells (20.3%) which were CD3+, fitted into the lymphocyte gate but showed a very low level of CD4 expression, comparable to that of monocytes. PMID: 9925966

  • Flow cytometric analysis of CD3/TCR complex, zinc, and glucocorticoid-mediated regulation of apoptosis and cell cycle distribution in thymocytes from old mice. PMID: 9581618

  • Using a flow cytometric method to detect dual-expression of surface proteins and intracellular components of the TCR/CD3 complex, we have studied 46 patients with myeloid malignancies. CD3-zeta expression was abnormal in 64% of patients, and was more prominent in those with advanced disease. PMID: 9531350

  • we have developed a flow cytometric technique for the simultaneous detection of surface (sCD3 epsilon) and cytoplasmic CD3 epsilon (cCD3 epsilon). PMID: 7851158

Immuno-Electron Microscopy (IEM)

  • In this study, we analyzed the distribution of CD3 and CD4 antigens at the ultrastructural level in tissue samples from mycosis fungoides patients using double-immunogold labeling. We observed clusters composed of CD3 and CD4 antigens on the plasma membrane and intracellular. PMID: 17013537

Immunofluorescence (IF)

  • Confocal laser scanning microscopy images showed that Kv1.3/FLAG channels and CD3 molecules accumulated in largely overlapping membrane areas. PMID: 12604782

  • Co-localization experiments applying antibody-induced co-capping and double immunofluorescence staining techniques were used to study the association of these fusion proteins with the TCR-CD3 complex, CD45 and CD28. PMID: 9368621

  • In an attempt to identify the phenotype of the CD25+ cells previously demonstrated in late-phase allergic reactions in skin and nasal mucosa, and in the bronchial mucosa in atopic asthma we have investigated the co-expression of CD3 and CD25 using double immunofluorescent staining. PMID: 1534311

Immunohistochemistry (IHC)

  • As CD7 is frequently deleted in mycosis fungoides (MF), immunohistochemical detection of T-cells was made using an antibody to CD3. Images of 100 CD3-positive cells per case in both groups were captured and analyzed using a simple computer program (Imagelab(R)) for nuclear perimeter (P), area (A), diameters (D) and nuclear contour index (NCI). PMID: 17496190

  • Immunohistochemistry for CD3, CD8, and CXCR3 was performed using liver biopsy specimens collected from the following 3 age-matched groups of patients. PMID: 16677891

  • Immunohistochemical detection of SWC3, CD2, CD3, CD4 and CD8 antigens in paraformaldehyde fixed and paraffin embedded porcine lymphoid tissue. PMID: 12909409

  • Immunohistochemistry analysis by cell immunophenotyping before and after a 3 - week treatment with naphthalan oil was performed on biopsy specimens from 10 patients with psoriasis vulgaris. For immunohistochemistry staining of 3- micro m paraffin block sections, anti-CD3, anti-CD4, anti-CD8, and Ki-67 antibodies were used. PMID: 12773261

  • In the present study, 13 cases of DCM in chronic alcoholics were investigated with qualification and quantification of infiltrating leucocytes using immunohistological antibodies against leucocyte common antigen (LCA), T-lymphocytes (CD3) and macrophages (CD68). PMID: 11955834

  • whilst immunohistochemical analyses demonstrated co-expression of B- and T-cell antigens (CD79a and CD3) by 95% of lymphomatous cells. PMID: 11778688

  • The CD3/TCR-bearing T cells in epidermis of human skin and cicatrix were examined by means of histomorphology and immunohistochemistry. PMID: 11501078

  • Using this optimized ImmunoMax method, we were able to detect CD2, CD3, CD4, and CD5 with conventional monoclonal antibodies in formalin-fixed, paraffin-embedded tissue specimens of various lymphoid tissues. PMID: 9389770

  • For standard evaluation of established inflammatory cell parameters such as CD3, CD4, CD8, and EG2, frozen tissue is preferable because of the ease of the method and its reliable cell counting. PMID: 9346185

  • we have used a recombinant fusion protein representing part of the epsilon subunit of the CD3 molecule to generate a novel monoclonal antibody (NCL-CD3-PS1) effective in paraffin sections. PMID: 9023553

  • we demonstrate that an antiserum recognizing a phylogenetically conserved part of the CD3 epsilon cytoplasmic tail detects T cells of many avian and mammalian species in formalin-fixed paraffin-embedded tissue sections. PMID: 8803615

  • Discordant CD3 expression in lymphomas when studied on frozen and paraffin sections. PMID: 7557948

  • The reactivity of eight preferential B-cell (L26, 4KB5, and KiB3) and T-cell (polyclonal CD3, Leu22, MT-1, UCHL-1, and OPD4) antibodies which detect paraffin-resistant antigens was examined by a three-step immunoperoxidase technique in 111 formalin-fixed, paraffin-embedded diffuse aggressive non-Hodgkin's lymphomas (NHLs) to determine the optimal panel for accurate lineage assignment. PMID: 8085550

  • Polyclonal rabbit antiserum to human T-cell CD3 was used to study its reactivity in lymphoid tissues (lymph nodes, spleen, aggregated lymphoid follicles [Peyer's patches], thymus) of several animal species (cattle, sheep, goats, rats, and mice). Using a peroxidase-antiperoxidase technique on formalin-fixed and paraffin-embedded tissues, immunoreactive cells were detected in T cell-dependent areas of the lymphoid tissues. PMID: 8141498

  • CD3 antigen expression was studied in a series of 98 T-cell lymphomas, using polyclonal antibodies which recognize this molecule in routinely processed, paraffin-embedded, tissue. PMID: 8514274

Immunoprecipitation (IP)

  • Immunoprecipitation showed that the antibody recognized a subset of CD3 molecules that were associated with gammadelta-TCR. PMID: 15885124

  • Immunoprecipitation and Western blotting studies demonstrated that this anti-CD3 bound to a single 23 kDa polypeptide, probably representing the koala homologue of the human epsilon chain. This is the first report of successful identification of koala T cells and the first reported use of this anti-CD3 for the identification of peripheral circulating T lymphocytes in any species. PMID: 8773202

Western Blot (WB)

  • Jurkat E-61 cells were incubated with the sera (20% volume to volume) and analyzed with Western immunoblot using mouse monoclonal CD3-zeta antibody. PMID: 14526327

  • The suppression of TcR/CD3-zeta expression on cultured T-lymphocytes (Jurkat cells) by sera and amniotic fluids from pregnant women was examined by Western immunoblots and quantitated by densitometry. PMID: 11839393

  • Biochemical demonstration of the low or absent CD3 zeta in PBMC from patients with RA was achieved by Western blot analysis. Immunohistochemical staining and image analysis also confirmed the low expression of zeta chains in synovial tissue of RA patients. PMID: 9519864