CD3e

Target id: 2742

Nomenclature: CD3e

Family: CD molecules

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: OFF :     CD3e has curated GtoImmuPdb data

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 207 11q23 CD3E CD3e molecule
Mouse - 183 9 A5 Cd3e CD3 antigen, epsilon polypeptide
Rat - 188 8q22 Cd3e CD3e molecule
Previous and Unofficial Names
Cde3 | CD3 antigen, epsilon polypeptide | CD3e molecule, epsilon (CD3-TCR complex) | CD3 molecule, epsilon | CD3 antigen
Database Links
CATH/Gene3D
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia

Download all structure-activity data for this target as a CSV file

Antibodies
Key to terms and symbols Click column headers to sort
Antibody Sp. Action Affinity Units Reference
blinatumomab Hs Binding 7.0 pKd 9
pKd 7.0 (Kd 1x10-7 M) [9]
Description: Binding of the single-chain Fv portion of blinatumomab to CD3.
muromonab-CD3 Hs Binding - - 10
[10]
catumaxomab Hs Binding - - 13
[13]
otelixizumab Hs Binding - - 3
[3]
Antibody Comments
Visilizumab (HuM291, Nuvion) is a humanized IgG2 anti-CD3e mAb that was engineered to prevent Fc receptor binding [17-18], a concept designed to minimise the mAb-induced cytokine release syndrome associated with exposure to conventional mAbs [6,14]. Visilizumab was developed as a potential immunosuppressive therapeutic for autoimmune diseases and as a prophylactic for transplant rejection. However this mAb failed to show significant clinical efficacy in kidney transplantation, psoriasis, GvHD and IDB, and development appears to have ceased. Visilizumab (humanized m291 IgG2M3 antibody claimed in US5834597) binds human CD3e with a Ka of 50nM [18].
Immunopharmacology Comments
CD3e is a subunit of the T cell receptor (TCR)-CD3 complex that mediates T cell receptor signal transduction in response to antigen detection. The TCR complex contains a CD3γ chain (CD3G), a CD3δ chain (CD3D), and two CD3ε chains (CD3E), plus the TCR (that can be α/β, or γ/δ type in the subsets of T cells named after the TCR they express) and the ζ-chain (zeta-chain).

CD3e plays a crucial role in T cell development, highlighted by the discovery that defects in CD3e cause severe immunodeficiency [7,16].

Therapeutic anti-CD3e monoclonal antibodies (mAbs) have been developed and investigated for clinically beneficial effects in autoimmune diseases (inflammatory bowel diseases [1,12] and type 1 diabetes [11,15]) and transplantation (graft-versus-host disease [4-5,19] and renal transplantation [14]) CD3e-targeting mAbs may be useful in combination with other therapies [2,8]. Anti-CD3e antibodies that are engineered to bind additional cellular targets and which selectively target the immune destruction of cancer cells are approved for use in immuno-oncology indications (e.g. blinatumomab and catumaxomab). Muromonab-CD3 was used to prevent rejection of organ allografts, but was withdrawn from the market due to lack of demand.
Cell Type Associations
Immuno Cell Type:  T cells
Immuno Process Associations
Immuno Process:  B cell (activation)
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0002250 adaptive immune response IEA
Immuno Process:  T cell (activation)
GO Annotations:  Associated to 6 GO processes
GO:0031295 T cell costimulation TAS
GO:0042102 positive regulation of T cell proliferation IMP
GO:0042110 T cell activation NAS
click arrow to show/hide IEA associations
GO:0002250 adaptive immune response IEA
GO:0045060 negative thymic T cell selection IEA
GO:0046641 positive regulation of alpha-beta T cell proliferation IEA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 6 GO processes
GO:0031295 T cell costimulation TAS
GO:0042102 positive regulation of T cell proliferation IMP
GO:0050776 regulation of immune response TAS
GO:0050852 T cell receptor signaling pathway TAS
click arrow to show/hide IEA associations
GO:0002669 positive regulation of T cell anergy IEA
GO:0046641 positive regulation of alpha-beta T cell proliferation IEA
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 3 GO processes
GO:0031295 T cell costimulation TAS
GO:0042102 positive regulation of T cell proliferation IMP
click arrow to show/hide IEA associations
GO:0046641 positive regulation of alpha-beta T cell proliferation IEA
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 6 GO processes
GO:0031295 T cell costimulation TAS
GO:0042102 positive regulation of T cell proliferation IMP
GO:0042110 T cell activation NAS
GO:0050852 T cell receptor signaling pathway TAS
click arrow to show/hide IEA associations
GO:0045060 negative thymic T cell selection IEA
GO:0046641 positive regulation of alpha-beta T cell proliferation IEA
Immuno Process:  Immune system development
GO Annotations:  Associated to 2 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0002669 positive regulation of T cell anergy IEA
GO:0045060 negative thymic T cell selection IEA
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 3 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0032729 positive regulation of interferon-gamma production IEA
GO:0032753 positive regulation of interleukin-4 production IEA
GO:0045086 positive regulation of interleukin-2 biosynthetic process IEA
Immuno Disease Associations
Disease Name:  Acute lymphocytic leukemia (ALL)
Disease Synonyms:  no synonynms
Comment:  CD3e is the molecular target of approved drug blinatumomab, as a treatment Philadelphia chromosome-negative precursor B-cell ALL
Disease X-refs:  OMIM: 613065
References: 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Immunodeficiency 18; IMD18
Synonyms: CD3epsilon deficiency [Disease Ontology: DOID:0060017]
Immunodeficiency 18, SCID variant [OMIM: 615615]
Immunodeficiency 18, Severe combined immunodeficiency variant [OMIM: 615615]
Severe combined immunodeficiency [Orphanet: ORPHA183660]
T-B+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta [Orphanet: ORPHA169160]
Disease Ontology: DOID:0060017
OMIM: 615615
Orphanet: ORPHA169160, ORPHA183660

References

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1. Ahluwalia JP. (2012) Immunotherapy in inflammatory bowel disease. Med. Clin. North Am., 96 (3): 525-44, x. [PMID:22703854]

2. Besançon A, Goncalves T, Valette F, Dahllöf MS, Mandrup-Poulsen T, Chatenoud L, You S. (2018) Oral histone deacetylase inhibitor synergises with T cell targeted immunotherapy to preserve beta cell metabolic function and induce stable remission of new-onset autoimmune diabetes in NOD mice. Diabetologia, 61 (2): 389-398. [PMID:29030662]

3. Bolt S, Routledge E, Lloyd I, Chatenoud L, Pope H, Gorman SD, Clark M, Waldmann H. (1993) The generation of a humanized, non-mitogenic CD3 monoclonal antibody which retains in vitro immunosuppressive properties. Eur. J. Immunol., 23 (2): 403-11. [PMID:8436176]

4. Carpenter PA, Appelbaum FR, Corey L, Deeg HJ, Doney K, Gooley T, Krueger J, Martin P, Pavlovic S, Sanders J et al.. (2002) A humanized non-FcR-binding anti-CD3 antibody, visilizumab, for treatment of steroid-refractory acute graft-versus-host disease. Blood, 99 (8): 2712-9. [PMID:11929757]

5. Carpenter PA, Lowder J, Johnston L, Frangoul H, Khoury H, Parker P, Jerome KR, McCune JS, Storer B, Martin P et al.. (2005) A phase II multicenter study of visilizumab, humanized anti-CD3 antibody, to treat steroid-refractory acute graft-versus-host disease. Biol. Blood Marrow Transplant., 11 (6): 465-71. [PMID:15931635]

6. Chau LA, Tso JY, Melrose J, Madrenas J. (2001) HuM291(Nuvion), a humanized Fc receptor-nonbinding antibody against CD3, anergizes peripheral blood T cells as partial agonist of the T cell receptor. Transplantation, 71 (7): 941-50. [PMID:11349730]

7. de Saint Basile G, Geissmann F, Flori E, Uring-Lambert B, Soudais C, Cavazzana-Calvo M, Durandy A, Jabado N, Fischer A, Le Deist F. (2004) Severe combined immunodeficiency caused by deficiency in either the delta or the epsilon subunit of CD3. J. Clin. Invest., 114 (10): 1512-7. [PMID:15546002]

8. Dean Y, Dépis F, Kosco-Vilbois M. (2012) Combination therapies in the context of anti-CD3 antibodies for the treatment of autoimmune diseases. Swiss Med Wkly, 142: w13711. [PMID:23254986]

9. Dreier T, Lorenczewski G, Brandl C, Hoffmann P, Syring U, Hanakam F, Kufer P, Riethmuller G, Bargou R, Baeuerle PA. (2002) Extremely potent, rapid and costimulation-independent cytotoxic T-cell response against lymphoma cells catalyzed by a single-chain bispecific antibody. Int. J. Cancer, 100 (6): 690-7. [PMID:12209608]

10. Goldstein G. (1987) Overview of the development of Orthoclone OKT3: monoclonal antibody for therapeutic use in transplantation. Transplant. Proc., 19 (2 Suppl 1): 1-6. [PMID:3105134]

11. Kaufman A, Herold KC. (2009) Anti-CD3 mAbs for treatment of type 1 diabetes. Diabetes Metab. Res. Rev., 25 (4): 302-6. [PMID:19319985]

12. Kawalec P, Mikrut A, Łopuch S. (2014) Systematic review of the effectiveness of biological therapy for active moderate to severe ulcerative colitis. J. Gastroenterol. Hepatol., 29 (6): 1159-70. [PMID:24955447]

13. Linke R, Klein A, Seimetz D. (2010) Catumaxomab: clinical development and future directions. MAbs, 2 (2): 129-36. [PMID:20190561]

14. Norman DJ, Vincenti F, de Mattos AM, Barry JM, Levitt DJ, Wedel NI, Maia M, Light SE. (2000) Phase I trial of HuM291, a humanized anti-CD3 antibody, in patients receiving renal allografts from living donors. Transplantation, 70 (12): 1707-12. [PMID:11152101]

15. Phillips B, Trucco M, Giannoukakis N. (2011) Current state of type 1 diabetes immunotherapy: incremental advances, huge leaps, or more of the same?. Clin. Dev. Immunol., 2011: 432016. [PMID:21785616]

16. Soudais C, de Villartay JP, Le Deist F, Fischer A, Lisowska-Grospierre B. (1993) Independent mutations of the human CD3-epsilon gene resulting in a T cell receptor/CD3 complex immunodeficiency. Nat. Genet., 3 (1): 77-81. [PMID:8490660]

17. Trajkovic V. (2002) Nuvion. Protein Design Labs. Curr Opin Investig Drugs, 3 (3): 411-4. [PMID:12054088]

18. Tso JY, Cole MS, Anasetti C. (1998) Mutated nonactivating IgG2 domains and anti CD3 antibodies incorporating the same. Patent number: US5834597. Assignee: Protein Design Labs Inc. Priority date: 20/05/1996. Publication date: 10/11/1998.

19. Yu XZ, Bidwell SJ, Martin PJ, Anasetti C. (2001) Anti-CD3 epsilon F(ab')2 prevents graft-versus-host disease by selectively depleting donor T cells activated by recipient alloantigens. J. Immunol., 166 (9): 5835-9. [PMID:11313428]

How to cite this page

CD molecules: CD3e. Last modified on 03/04/2018. Accessed on 17/07/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2742.