CD28
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| Location (UCSC) | Chr 2: 203.71 – 203.74 Mb | Chr 1: 60.76 – 60.81 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
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CD28 (Cluster of Differentiation 28) is one of the
CD28 is the receptor for
CD28 is the only
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.
As a homodimer of two chains with Ig domains binds B7 molecules on APCs and it can promotes T cells proliferation and differentiation, stimulates production of growth factors and induces the expression of anti-apoptotic proteins.[10] According to several studies, after birth, all human cells express CD28. But in adult, 20-30% of CD8+ T cells lose the ability of CD28 expression, whereas in the elderly (+80 years) up to 50-60% of CD8+ cells lose the ability of CD28 expression.[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 underlined 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]
Signaling
CD28 possesses an intracellular domain with several residues that are critical for its effective signaling. The YMNM motif beginning at
CD28 also contains two
Structure
The first structure of CD28 was obtained in 2005 by the T-cell biology group at the University of Oxford.[18]
The structure of the CD28 protein contains 220 amino acids, encoded by a gene consisting of four exons. It is a glycosylated, disulfide-linked homodimer of 44 kDa expressed on the cell surface. The structure contains paired domains of the V-set immunoglobulin superfamilies (IgSF). These domains are linked to individual transmembrane domains and cytoplasmic domains that contain critical signaling motifs.
CD28 family members
CD28 belongs into group members of a subfamily of costimulatory molecules that are characterized by an extracellular variable immunoglobulin-like domain. Members of this subfamily also include homologous receptors
As a drug target
The drug
It is known that CD28 and CTL4 may be critical regulators of autoimmune diseases in mouse model.[29][30] But there is less data from patients on the role of CD28 in human diseases.
Other potential drugs in pre-clinical development are agonist CD28 aptamers with immunostimulatory properties in a mouse tumor model,[31] a monoclonal anti-CD28 Fab´ antibody FR104,[32] or an octapeptide AB103, which prevents CD28 homodimerization.[33]
Interactions
CD28 has been shown to
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000178562 – Ensembl, May 2017
- ^ a b c GRCm38: 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.
- S2CID 22737782.
- PMID 21690252.
- S2CID 22349635.
- S2CID 21120027.
- PMID 21745657.
- PMID 27192564.
- PMID 8881749.
- PMID 10692235.
- OCLC 1031053171.)
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- PMID 8146197.
- S2CID 23540587.
- PMID 21964608.
- ^ S2CID 23630078.
- PMID 11861596.
- PMID 12606712.
- PMID 23470321.
- PMID 2164219.
- S2CID 7990944.
- PMID 7543139.
- PMID 7882171.
- PMID 19217324.
- PMID 10449520.
- S2CID 10820672.
- PMID 10795741.
- S2CID 46680106.
- PMID 23756353.
- S2CID 715661.
- PMID 25054224.
- S2CID 25739159.
- S2CID 39280280.
- S2CID 37740924.
- S2CID 12566111.
Further reading
- Esensten JH, Helou YA, Chopra G, Weiss A, Bluestone JA (May 2016). "CD28 Costimulation: From Mechanism to Therapy". Immunity. 44 (5): 973–88. PMID 27192564.
- Lenschow DJ, Walunas TL, Bluestone JA (1996). "CD28/B7 system of T cell costimulation". Annual Review of Immunology. 14: 233–58. PMID 8717514.
- Greenfield EA, Nguyen KA, Kuchroo VK (1998). "CD28/B7 costimulation: a review". Critical Reviews in Immunology. 18 (5): 389–418. PMID 9784967.
- Chang TT, Kuchroo VK, Sharpe AH (2002). "Role of the B7-CD28/CTLA-4 pathway in autoimmune disease". Signal Transduction Pathways in Autoimmunity. Current Directions in Autoimmunity. Vol. 5. pp. 113–30. )
- Bour-Jordan H, Blueston JA (January 2002). "CD28 function: a balance of costimulatory and regulatory signals". Journal of Clinical Immunology. 22 (1): 1–7. S2CID 38060684.
- Greenway AL, Holloway G, McPhee DA, Ellis P, Cornall A, Lidman M (April 2003). "HIV-1 Nef control of cell signalling molecules: multiple strategies to promote virus replication". Journal of Biosciences. 28 (3): 323–35. S2CID 33749514.
- Bénichou S, Benmerah A (January 2003). "[The HIV nef and the Kaposi-sarcoma-associated virus K3/K5 proteins: "parasites"of the endocytosis pathway]". Médecine/Sciences. 19 (1): 100–6. PMID 12836198.
- Tolstrup M, Ostergaard L, Laursen AL, Pedersen SF, Duch M (April 2004). "HIV/SIV escape from immune surveillance: focus on Nef". Current HIV Research. 2 (2): 141–51. PMID 15078178.
- Anderson JL, Hope TJ (April 2004). "HIV accessory proteins and surviving the host cell". Current HIV/AIDS Reports. 1 (1): 47–53. S2CID 34731265.
- Li L, Li HS, Pauza CD, Bukrinsky M, Zhao RY (2006). "Roles of HIV-1 auxiliary proteins in viral pathogenesis and host-pathogen interactions". Cell Research. 15 (11–12): 923–34. S2CID 24253878.
- Stove V, Verhasselt B (January 2006). "Modelling thymic HIV-1 Nef effects". Current HIV Research. 4 (1): 57–64. PMID 16454711.
External links
- Mouse CD Antigen Chart
- Human CD Antigen Chart
- Human CD28 genome location and CD28 gene details page in the UCSC Genome Browser.
- Overview of all the structural information available in the PDB for UniProt: P10747 (T-cell-specific surface glycoprotein CD28) at the PDBe-KB.
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