CD28

Target id: 2863

Nomenclature: CD28

Family: Other immune checkpoint proteins, 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 :     CD28 has curated GtoImmuPdb data

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 220 2q33 CD28 CD28 molecule
Mouse 1 218 1 C1-C3 Cd28 CD28 antigen
Rat 1 218 9q31 Cd28 Cd28 molecule
Previous and Unofficial Names
cluster of differentiation 28 | CD28 antigen (Tp44)
Database Links
CATH/Gene3D
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
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
lulizumab pegol Hs Binding 9.3 – 9.4 pKd 3
pKd 9.3 – 9.4 (Kd 5.1x10-10 – 3.6x10-10 M) [3]
Description: Note that this Kd value was determined using the 'naked' binding component, in the absence of PEGylation.
Immunopharmacology Comments
CD28 is expressed on the surface of T cells and is required for the co-stimulatory signal essential for the activation, proliferation and survival of T cells, and Th2 cell development. CD28 acts in concert with the T cell receptor to stimulate cytokine release (promotes IL-2 production). CD28 binds the the B7 proteins CD80 and CD86 on the surface of antigen presenting cells to effect a co-stimulatory signal to T cells. In contrast, CTLA-4 delivers a co-inhibitory signal via CD80/CD86 [1]. These two opposing signals are part of a complex network of positive and negative co-stimulatory signals, that integrate to modulate immune responses.
As a drug target, CD28 modulation is being investigated as a treatment for autoimmume conditions. In 2006 an anti-CD28 antbody with superagonist activity (TGN1412) caused catastrophic organ failure in clinical trial participants due to 'cytokine storm' (multiple cytokine-release syndrome) in response to massive systemic T cell activation and inflammatory response [4]. More recently developed anti-CD28 antibodies are modified in ways which prevent co-stimulation and cytokine release, and result only in T cell anergy or apoptosis [3]. FR104, an antagonist anti-CD28 monovalent fab' antibody, has reported efficacy as an alternative immunosuppression strategy to B7 antagonists for kidney transplant recipients [2]. FR104 has completed a Phase 1 first-in-human trial (NCT02800811) in healthy subjects.
Immuno Cell Type Associations
Immuno Cell Type:  T cells
Cell Ontology Term:  
Comment: 
References: 
Immuno Process Associations
Immuno Process:  T cell (activation)
Immuno Process ID:  4
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  T cell costimulation (GO:0031295) TAS
positive regulation of T cell proliferation (GO:0042102) IDA
negative thymic T cell selection (GO:0045060) IEA
regulatory T cell differentiation (GO:0045066) IDA
regulation of regulatory T cell differentiation (GO:0045589) IEA
positive regulation of alpha-beta T cell proliferation (GO:0046641) IEA
positive regulation of isotype switching to IgG isotypes (GO:0048304) IEA
References: 
Immuno Process:  Immune regulation
Immuno Process ID:  6
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  positive regulation of inflammatory response to antigenic stimulus (GO:0002863) IEA
T cell costimulation (GO:0031295) TAS
positive regulation of T cell proliferation (GO:0042102) IDA
regulation of regulatory T cell differentiation (GO:0045589) IEA
positive regulation of alpha-beta T cell proliferation (GO:0046641) IEA
positive regulation of isotype switching to IgG isotypes (GO:0048304) IEA
T cell receptor signaling pathway (GO:0050852) IEA
References: 
Immuno Process:  Immune system development
Immuno Process ID:  8
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  negative thymic T cell selection (GO:0045060) IEA
regulatory T cell differentiation (GO:0045066) IDA
regulation of regulatory T cell differentiation (GO:0045589) IEA
positive regulation of isotype switching to IgG isotypes (GO:0048304) IEA
References: 
Immuno Process:  Cytokine production & signalling
Immuno Process ID:  9
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  positive regulation of interleukin-10 production (GO:0032733) IDA
positive regulation of interleukin-4 production (GO:0032753) IDA
interleukin-7-mediated signaling pathway (GO:0038111) TAS
cytokine biosynthetic process (GO:0042089) TAS
positive regulation of interleukin-2 biosynthetic process (GO:0045086) IDA
References: 
Immuno Process:  Chemotaxis & migration
Immuno Process ID:  10
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  T cell costimulation (GO:0031295) TAS
positive regulation of T cell proliferation (GO:0042102) IDA
regulation of regulatory T cell differentiation (GO:0045589) IEA
positive regulation of alpha-beta T cell proliferation (GO:0046641) IEA
References: 
Immuno Process:  Cellular signalling
Immuno Process ID:  11
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  T cell costimulation (GO:0031295) TAS
positive regulation of T cell proliferation (GO:0042102) IDA
negative thymic T cell selection (GO:0045060) IEA
regulatory T cell differentiation (GO:0045066) IDA
regulation of regulatory T cell differentiation (GO:0045589) IEA
positive regulation of alpha-beta T cell proliferation (GO:0046641) IEA
positive regulation of isotype switching to IgG isotypes (GO:0048304) IEA
T cell receptor signaling pathway (GO:0050852) IEA
References: 
Immuno Process:  Inflammation
Immuno Process ID:  2
Comment: 
GO Annotation:  Associated to GO processes, IEA only
GO Processes:  positive regulation of inflammatory response to antigenic stimulus (GO:0002863) IEA
positive regulation of isotype switching to IgG isotypes (GO:0048304) IEA
References: 
Immuno Process:  B cell (activation)
Immuno Process ID:  5
Comment: 
GO Annotation:  Associated to GO processes, IEA only
GO Processes:  positive regulation of isotype switching to IgG isotypes (GO:0048304) IEA
References: 

References

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1. Alegre ML, Frauwirth KA, Thompson CB. (2001) T-cell regulation by CD28 and CTLA-4. Nat. Rev. Immunol.1 (3): 220-8. [PMID:11905831]

2. Poirier N, Dilek N, Mary C, Ville S, Coulon F, Branchereau J, Tillou X, Charpy V, Pengam S, Nerriere-Daguin V et al.. (2015) FR104, an antagonist anti-CD28 monovalent fab' antibody, prevents alloimmunization and allows calcineurin inhibitor minimization in nonhuman primate renal allograft. Am. J. Transplant.15 (1): 88-100. [PMID:25488654]

3. Suchard SJ, Davis PM, Kansal S, Stetsko DK, Brosius R, Tamura J, Schneeweis L, Bryson J, Salcedo T, Wang H et al.. (2013) A monovalent anti-human CD28 domain antibody antagonist: preclinical efficacy and safety. J. Immunol.191 (9): 4599-610. [PMID:24081989]

4. Suntharalingam G, Perry MR, Ward S, Brett SJ, Castello-Cortes A, Brunner MD, Panoskaltsis N. (2006) Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. N. Engl. J. Med.355 (10): 1018-28. [PMID:16908486]

How to cite this page

CD molecules: CD28. Last modified on 10/08/2017. Accessed on 16/12/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2863.