positive regulation of alpha-beta T cell proliferation
immune response
apoptotic signaling pathway
positive regulation of phosphatidylinositol 3-kinase signaling
positive regulation of isotype switching to IgG isotypes
positive regulation of viral genome replication
T cell receptor signaling pathway
positive regulation of mitotic nuclear division
positive regulation of inflammatory response to antigenic stimulus
positive regulation of transcription by RNA polymerase II
positive regulation of interleukin-10 production
phosphatidylinositol phosphate biosynthetic process
positive regulation of interleukin-4 production
positive regulation of protein kinase B signaling
T cell activation
negative regulation of apoptotic process
regulation of T cell proliferation
immune system process
Sources:Amigo / QuickGO
Orthologs
Species
Human
Mouse
Entrez
940
12487
Ensembl
ENSG00000178562
ENSMUSG00000026012
UniProt
P10747
P31041
RefSeq (mRNA)
NM_001243077 NM_001243078 NM_006139
NM_007642
RefSeq (protein)
NP_001230006 NP_001230007 NP_006130
NP_031668
Location (UCSC)
Chr 2: 203.71 – 203.74 Mb
Chr 1: 60.76 – 60.81 Mb
PubMed search
[3]
[4]
Wikidata
View/Edit Human
View/Edit Mouse
CD28 (Cluster of Differentiation 28) is one of the proteins expressed on T cells that provide co-stimulatory signals required for T cell activation and survival. T cell stimulation through CD28 in addition to the T-cell receptor (TCR) can provide a potent signal for the production of various interleukins (IL-6 in particular).
CD28 is the receptor for CD80 (B7.1) and CD86 (B7.2) proteins. When activated by Toll-like receptor ligands, the CD80 expression is upregulated in antigen-presenting cells (APCs). The CD86 expression on antigen-presenting cells is constitutive (expression is independent of environmental factors).
CD28 is the only B7 receptor constitutively expressed on naive T cells. Association of the TCR of a naive T cell with MHC:antigen complex without CD28:B7 interaction results in a T cell that is anergic.
Furthermore, CD28 was also identified on bone marrow stromal cells, plasma cells, neutrophils and eosinophils, but the functional importance of CD28 on these cells is not completely understood.[5][6][7][8] It is generally reported, that CD28 is expressed on 50% of CD8+ T cells and more than 80% CD4+ T cells in human, but during the course of activation some T cells lose this molecule. Some antigen-experienced T cells lose CD28 and subsequently can be re-activated without CD28 engagement. These CD28− T cells have generally been characterized as antigen specific and terminally differentiated, and are often described as being memory T cells (TMs). In addition, the level of positive CD28 decreases with age.[9]
As a homodimer of two chains with Ig domains, CD28 binds B7 molecules on APCs and can promote T cells proliferation and differentiation, stimulate production of growth factor, and induces the expression of anti-apoptotic proteins.[10]
According to several studies, after birth, all human cells express CD28. However, in adults, 20-30% of CD8+ T cells lose CD28 expression, whereas in the elderly (+80 years) up to 50-60% of CD8+ cells lose the ability to express CD28.[11] But these statements only suggest that loss of CD28 expression marks functional differentiation to cytotoxic memory cells within clonal expansions.[12]
In general, CD28 is a primary costimulatory molecule for T cell activation, but effective co-stimulation is essential only for some T cell activation. In this case, in the absence of co-stimulatory signals, the interaction of dendritic and T cells leads to T cell anergy. The importance of the costimulatory pathway is emphasized by the fact that antagonists of co-stimulatory molecules disrupt the immune responses both in vitro and in vivo.[13] But as mentioned earlier, during the course of activation e.g. TMs lose this molecule and assume a CD28-independent existence.[14]
^ abcGRCh38: Ensembl release 89: ENSG00000178562 – Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000026012 – Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Gray Parkin, Kirstin; Stephan, Robert P.; Apilado, Ron-Gran; Lill-Elghanian, Deborah A.; Lee, Kelvin P.; Saha, Bhaskar; Witte, Pamela L. (2002-09-01). "Expression of CD28 by Bone Marrow Stromal Cells and Its Involvement in B Lymphopoiesis". The Journal of Immunology. 169 (5): 2292–2302. doi:10.4049/jimmunol.169.5.2292. ISSN 0022-1767. PMID 12193694. S2CID 22737782.
^Rozanski, Cheryl H.; Arens, Ramon; Carlson, Louise M.; Nair, Jayakumar; Boise, Lawrence H.; Chanan-Khan, Asher A.; Schoenberger, Stephen P.; Lee, Kelvin P. (2011-06-20). "Sustained antibody responses depend on CD28 function in bone marrow–resident plasma cells". Journal of Experimental Medicine. 208 (7): 1435–1446. doi:10.1084/jem.20110040. ISSN 1540-9538. PMC 3135367. PMID 21690252.
^Venuprasad, K.; Parab, Pradeep; Prasad, D. V. R.; Sharma, Satyan; Banerjee, Pinaki P.; Deshpande, Manisha; Mitra, Dipendra K.; Pal, Subrata; Bhadra, Ranjan; Mitra, Debashis; Saha, Bhaskar (May 2001). <1536::aid-immu1536>3.0.co;2-8 "Immunobiology of CD28 expression on human neutrophils. I. CD28 regulates neutrophil migration by modulating CXCR-1 expression". European Journal of Immunology. 31 (5): 1536–1543. doi:10.1002/1521-4141(200105)31:5<1536::aid-immu1536>3.0.co;2-8. ISSN 0014-2980. PMID 11465111. S2CID 22349635.
^Woerly, G.; Decot, V.; Loiseau, S.; Loyens, M.; Chihara, J.; Ono, N.; Capron, M. (September 2004). "CD28 and secretory immunoglobulin A-dependent activation of eosinophils: inhibition of mediator release by the anti-allergic drug, suplatast tosilate". Clinical & Experimental Allergy. 34 (9): 1379–1387. doi:10.1111/j.1365-2222.2004.02036.x. ISSN 0954-7894. PMID 15347370. S2CID 21120027.
^Diaz, David; Chara, Luis; Chevarria, Julio; Ubeda, Maria; Muñoz, Leticia; Barcenilla, Hugo; Sánchez, Miguel Angel; Moreno, Zaida; Monserrat, Jorge; Albillos, Agustin; Prieto, Alfredo (2011). "Loss of surface antigens is a conserved feature of apoptotic lymphocytes from several mammalian species". Cellular Immunology. 271 (1): 163–172. doi:10.1016/j.cellimm.2011.06.018. ISSN 0008-8749. PMID 21745657.
^Esensten, Jonathan H.; Helou, Ynes A.; Chopra, Gaurav; Weiss, Arthur; Bluestone, Jeffrey A. (May 2016). "CD28 Costimulation: From Mechanism to Therapy". Immunity. 44 (5): 973–988. doi:10.1016/j.immuni.2016.04.020. PMC 4932896. PMID 27192564.
^FAGNONI, F. F.; VESCOVINI, R.; MAZZOLA, M.; BOLOGNA, G.; NIGRO, E.; LAVAGETTO, G.; FRANCESCHI, C.; PASSERI, M.; SANSONI, P. (August 1996). "Expansion of cytotoxic CD8 + CD28 − T cells in healthy ageing people, including centenarians". Immunology. 88 (4): 501–507. doi:10.1046/j.1365-2567.1996.d01-689.x. ISSN 0019-2805. PMC 1456634. PMID 8881749.
^Chamberlain, Winston D.; Falta, Michael T.; Kotzin, Brian L. (March 2000). "Functional Subsets within Clonally Expanded CD8+ Memory T Cells in Elderly Humans". Clinical Immunology. 94 (3): 160–172. doi:10.1006/clim.1999.4832. PMID 10692235.
^Chapel, Helen (2018). Základy klinické imunologie : 6. vydání. Mansel Haeney, Siraj A. Misbah, Neil Snowden, Vojtěch Thon. Praha. ISBN 978-80-7553-396-8. OCLC 1031053171.{{cite book}}: CS1 maint: location missing publisher (link)
^Mou, D.; Espinosa, J.; Lo, D. J.; Kirk, A. D. (November 2014). "CD28 Negative T Cells: Is Their Loss Our Gain?: CD28 Negative T Cells". American Journal of Transplantation. 14 (11): 2460–2466. doi:10.1111/ajt.12937. PMC 4886707. PMID 25323029.
CD28 (Cluster of Differentiation 28) is one of the proteins expressed on T cells that provide co-stimulatory signals required for T cell activation and...
Theralizumab (also known as TGN1412, CD28-SuperMAB, and TAB08) is an immunomodulatory drug developed by Thomas Hünig of the University of Würzburg. It...
works in tandem. Both CD80 and CD86 interact with costimulatory receptors CD28, CTLA-4 (CD152) and the p75 neurotrophin receptor . CD80 is a member of the...
CD28 family receptors are a group of regulatory cell surface receptors expressed on immune cells. The CD28 family in turn is a subgroup of the immunoglobulin...
CTLA-4 in mice, its conservation in humans and similarities with CD28 were soon noticed. CD28 at that time was a recently identified "T cell costimulatory"...
molecule CD28 on the surface of all naïve T cells, and to the inhibitory receptor CTLA-4 (cytotoxic T-lymphocyte antigen-4, also known as CD152). CD28 and...
significant remissions. In the early 2000s, co-stimulatory domains such as CD28 or 4-1BB were added to first generation CAR's CD3ζ intracellular domain....
Acazicolcept (ALPN-101) is an experimental dual CD28/ICOS antagonist developed by AbbVie. Yang, Jing; Lickliter, Jason D.; Hillson, Jan L.; Means, Gary...
simultaneous engagement of the T-cell receptor and a co-stimulatory molecule (like CD28, or ICOS) on the T cell by the major histocompatibility complex (MHCII) peptide...
pathways: NFAT, NFkB and AP-1. In addition and after costimulation from CD28 the optimal activation of expression of IL-2 and these pathways is induced...
receptors which is not constitutively expressed on resting naïve T cells, unlike CD28. OX40 is a secondary co-stimulatory immune checkpoint molecule, expressed...
Another two stimulatory checkpoint molecules belong to the B7-CD28 superfamily—CD28 itself and ICOS. CD27: This molecule supports antigen-specific expansion...
interaction between CD28 on the CD4+ T cell and the proteins CD80 (B7.1) or CD86 (B7.2) on the professional APCs. Both CD80 and CD86 activate the CD28 receptor....
up to 20% of the body's T-cells. Furthermore, Anti-CD3 and Anti-CD28 antibodies (CD28-SuperMAB) have also shown to be highly potent superantigens (and...
successfully substitute the CD28 requirement during autoimmunity. In an autoimmune background CD4+ T cells bypass the requirement of CD28 cosignaling to become...
co-stimulate human CD28− T cells and trigger the increase in CD28− T cells. Unlike the activation of CD8+ T cells, the proliferation of CD28− T cells can negatively...
the ICOS (Inducible T-cell COStimulator) gene. The protein belongs to the CD28 and CTLA-4 cell-surface receptor family. These are proteins expressed on...
the APC must present a B7 protein (CD80 or CD86) on its cell surface to a CD28 protein on the surface of the T cell. These two signals activate the T cell...
coreceptor and the class I MHC molecule to stabilize this signal. Second Signal CD28 molecule on the T cell either CD80 or CD86 (also called B7-1 and B7-2) CD80...
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