CD28

CD28
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1YJD, 3WA4, 5AUL
Identifiers
Aliases	CD28, Tp44, CD28 molecule
External IDs	OMIM: 186760; MGI: 88327; HomoloGene: 4473; GeneCards: CD28; OMA:CD28 - orthologs
Gene location (Human) Chr. Chromosome 2 (human)[1] Band 2q33.2 Start 203,706,475 bp[1] End 203,738,912 bp[1]
Gene location (Mouse) Chr. Chromosome 1 (mouse)[2] Band 1 C2|1 30.52 cM Start 60,755,959 bp[2] End 60,812,518 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in lymph node appendix blood granulocyte epithelium of colon gallbladder amniotic fluid thymus tonsil spleen Top expressed in thymus blood spleen vastus lateralis muscle mesenteric lymph nodes triceps brachii muscle temporal muscle subcutaneous adipose tissue sternocleidomastoid muscle morula More reference expression data BioGPS More reference expression data
Gene ontology Molecular function coreceptor activity protease binding protein binding identical protein binding protein kinase binding phosphatidylinositol-4,5-bisphosphate 3-kinase activity Cellular component integral component of membrane cytosol membrane plasma membrane integral component of plasma membrane immunological synapse external side of plasma membrane cell surface protein complex involved in cell adhesion Biological process regulatory T cell differentiation regulation of regulatory T cell differentiation T cell costimulation mitigation of host defenses by virus positive regulation of translation negative regulation of gene expression negative thymic T cell selection cell surface receptor signaling pathway positive regulation of gene expression humoral immune response positive regulation of T cell proliferation 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
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CD28 (Cluster of Differentiation 28) is a protein expressed on T cells that provides essential co-stimulatory signals required for T cell activation and survival. When T cells are stimulated through CD28 in conjunction with the T-cell receptor (TCR), it enhances the production of various interleukins, particularly IL-6. CD28 serves as a receptor for CD80 (B7.1) and CD86 (B7.2), proteins found on antigen-presenting cells (APCs).

CD28 is the only B7 receptor consistently expressed on naive T cells. In the absence of CD28:B7 interaction, a naive T cell's TCR engagement with an MHC:antigen complex leads to anergy. CD28 is also expressed on bone marrow stromal cells, plasma cells, neutrophils, and eosinophils, although its function in these cells is not fully understood.^[5]

Typically, CD28 is expressed on about 50% of CD8+ T cells and more than 80% of CD4+ T cells in humans. However, some T cells lose CD28 expression during activation, particularly antigen-experienced T cells, which can be re-activated independently of CD28. These CD28⁻ T cells are often antigen-specific, terminally differentiated, and categorized as memory T cells (TMs). The proportion of CD28⁻ T cells increases with age.^[6]

As a homodimer with Ig domains, CD28 binds B7 molecules on APCs, promoting T cell proliferation, differentiation, growth factor production, and the expression of anti-apoptotic proteins.^[7] While CD28 is crucial for T cell activation, particularly in initial immune responses, some antigen-experienced T cells can function without it, marking their differentiation into cytotoxic memory cells.^[8]