Gene Ontology annotation through association of InterPro records with GO terms
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping
Gene Ontology annotation based on curation of immunofluorescence data
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Electronic Gene Ontology annotations created by ARBA machine learning models
B-cell surface antigen B7 provides a costimulatory signal that induces T cells to proliferate and secrete interleukin 2.
-
Foundational demonstration of B7-CD28 costimulation driving T cell proliferation and IL-2 secretion
"B7-transfected CHO cells can induce suboptimally activated CD28+ T cells to proliferate and secrete high levels of interleukin 2"
Human T cell activation. II. A new activation pathway used by a major T cell population via a disulfide-bonded dimer of a 44 kilodalton polypeptide (9.3 antigen).
-
One of the earliest demonstrations of anti-CD28 antibody-mediated T cell costimulation
"mAb 9.3 was capable of inducing T cell proliferation in the presence of 12-o-tetradecanoyl phorbol-13-acetate (TPA)"
Involvement of T44 molecules in an antigen-independent pathway of T cell activation. Analysis of the correlations to the T cell antigen-receptor complex.
Identification of residues in the V domain of CD80 (B7-1) implicated in functional interactions with CD28 and CTLA4.
-
Identified hydrophobic residues in CD80 critical for CD28 and CTLA-4 binding
"Two hydrophobic residues in the V-like domain of CD80 were identified as critical for binding to CD28 and are also important for the interaction with CTLA4"
-
Y87 in CD80 is conserved across species and important for CD28 interaction
"One of these residues, Y87, is conserved in all CD80 and CD86 cloned from various species"
p56Lck and p59Fyn regulate CD28 binding to phosphatidylinositol 3-kinase, growth factor receptor-bound protein GRB-2, and T cell-specific protein-tyrosine kinase ITK: implications for T-cell costimulation.
-
Demonstrated Lck-dependent phosphorylation of CD28 Tyr-191
"p56Lck and p59Fyn phosphorylate CD28 primarily at Tyr-191 of the Tyr-Met-Asn-Met motif, inducing a 3- to 8-fold increase in p85 (subunit of PI 3-kinase) and GRB-2 SH2 binding to CD28"
-
CD28 binds PI3K, GRB2, and ITK through the YMNM motif
"CD28 interacts with three intracellular proteins-phosphatidylinositol 3-kinase (PI 3-kinase), T cell-specific protein-tyrosine kinase ITK (formerly TSK or EMT), and the complex between growth factor receptor-bound protein 2 and son of sevenless guanine nucleotide exchange protein (GRB-2-SOS)"
Selective CD28pYMNM mutations implicate phosphatidylinositol 3-kinase in CD86-CD28-mediated costimulation.
-
Y191 mutation disrupts both PI3K and GRB2 binding
"Y191 mutation (Y191CD28F) disrupted both PI 3-kinase and GRB-2 binding"
-
M194 mutation selectively disrupts PI3K binding
"M194 mutation (M194CD28C) disrupted only PI 3-kinase binding"
-
Both mutations abolished IL-2 production, directly implicating PI3K in CD28 costimulation
"Both Y191CD28F and M194CD28C mutants failed to generate IL-2. These data directly implicate PI 3-kinase in CD28-mediated costimulation leading to IL-2 secretion"
CTLA-4 binding to the lipid kinase phosphatidylinositol 3-kinase in T cells.
-
Compared CD28 and CTLA-4 binding to PI3K p85 SH2 domains
"CTLA-4 can also associate with PI 3-kinase as detected by lipid kinase analysis and immunoblotting with anti-p85 antiserum"
-
Similar binding affinity of p85 SH2 domains for CD28 and CTLA-4 cytoplasmic motifs
"the NH2- and COOH-terminal SH2 domains of p85 bind the CTLA-4 cytoplasmic pYVKM motif with an affinity (ID50: 0.6 and 0.04 microM), that is similar to CD28"
Cross-linking of the CD40 ligand on human CD4+ T lymphocytes generates a costimulatory signal that up-regulates IL-4 synthesis.
-
CD28 costimulation with CD3 and CD40L greatly enhances IL-4 synthesis
"IL-4 synthesis was greatly enhanced by triggering of CD40L on the T cell surface in conjunction with ligation of CD3/TCR and CD28"
-
CD28 alone with CD3 produces little IL-4 without CD40L
"ligation of CD3/TCR and CD28 in the absence of CD40L triggering resulted in little or no IL-4 synthesis"
CD28/B7 system of T cell costimulation.
-
CD28 promotes cytokine production and inhibits apoptosis
"The CD28/B7 receptor/ligand system is one of the dominant costimulatory pathways. Interruption of this signaling pathway with CD28 antagonists not only results in the suppression of the immune response, but in some cases induces antigen-specific tolerance"
Growth factor receptor-bound protein 2 SH2/SH3 domain binding to CD28 and its role in co-signaling.
-
Both GRB2 SH2 and SH3 domains contribute to CD28 binding
"the Grb2 SH2 domain is critical for the association, while the SH3 domain plays an additional role in facilitating optimal binding"
-
GRB2 binding to CD28 is required for IL-2 production and Vav phosphorylation
"Mutations that alter Grb2 binding were found to block the CD28-dependent interleukin-2 production. Further, tyrosine phosphorylation of Vav and the costimulation-dependent activation of Jun N-terminal kinase was blocked"
-
CD28/GRB2 interaction is required for JNK activation
"the costimulation-dependent activation of Jun N-terminal kinase was blocked in cells defective in CD28/Grb2 binding"
CD28/B7 costimulation: a review.
-
Comprehensive review of CD28 as a costimulatory receptor
"The current model of T cell activation requires two signals. The first signal is specific, requiring T cell receptor recognition and binding to MHC/Antigen presented by an antigen-presenting cell. The second signal is nonspecific, resulting from the binding of B7 ligand on the antigen-presenting cell with its receptor, CD28, on the T cell"
GRID: a novel Grb-2-related adapter protein that interacts with the activated T cell costimulatory receptor CD28.
Structural basis for co-stimulation by the human CTLA-4/B7-2 complex.
-
3.2A crystal structure of CTLA-4/B7-2 complex
"we report the 3.2-A resolution structure of the complex between the disulphide-linked homodimer of human CTLA-4 and the receptor-binding domain of human B7-2"
-
Provides structural basis for understanding CD28/CTLA-4 engagement with B7 ligands
"Regulation of T-cell activity is dependent on antigen-independent co-stimulatory signals provided by the disulphide-linked homodimeric T-cell surface receptors, CD28 and CTLA-4"
Mechanism for down-regulation of CD28 by Nef.
The transmembrane adaptor protein TRIM regulates T cell receptor (TCR) expression and TCR-mediated signaling via an association with the TCR zeta chain.
-
Confirmed CD28 cell surface expression on T cells
"T cell receptor (TCR)-interacting molecule (TRIM) is a recently identified transmembrane adaptor protein, which is exclusively expressed in T cells"
The interaction properties of costimulatory molecules revisited.
-
Characterized CD28 binding to CD80 and CD86
"B7-2 binds the two receptors more weakly than B7-1"
-
Demonstrated CD28 stimulation increases proliferation and cytokine expression
"relative to its CTLA-4 binding affinity, B7-2 binds CD28 2- to 3-fold more effectively than B7-1"
The modulation of CD40 ligand signaling by transmembrane CD28 splice variant in human T cells.
-
Isoform 3 (CD28i) interacts with CD40LG and enhances NF-kB and MAPK8/PAK2 activation
"In this study we show that CD28i, a transmembrane splice variant of CD28 costimulatory receptor, complexes with CD40L in human T cells"
-
CD28i localizes to the cell surface
"CD28i is unique among other isoforms as it retains an intact transmembrane region and cytoplasmic tail, but lacks the B7 ligand binding motif"
Characterization of Lck-binding elements in the herpesviral regulatory Tip protein.
-
Characterized Lck SH3 and SH2 domain binding properties (CD28 used as reference)
"Herpesvirus saimiri encodes a tyrosine kinase interacting protein (Tip) that binds to T-cell-specific tyrosine kinase Lck via multiple sequence motifs and controls its activity"
CCL5-mediated T-cell chemotaxis involves the initiation of mRNA translation through mTOR/4E-BP1.
-
Focus on CCL5 signaling in T cells, not directly on CD28
"we examined the role for CCL5-mediated initiation of mRNA translation in CD4(+) T-cell chemotaxis"
Acquisition of suppressive function by activated human CD4+ CD25- T cells is associated with the expression of CTLA-4 not FoxP3.
-
CTLA-4 is the key determinant for Treg suppressive function
"the acquisition of suppressive behavior by activated CD4(+)CD25(-) T cells requires the expression of CTLA-4"
-
CD28-dependent T cell activation leads to CTLA-4 and FoxP3 induction
"Activation of human CD4(+)CD25(-) T cells resulted in the appearance of a de novo population of FoxP3-expressing cells within 48 h. These cells expressed high levels of CTLA-4"
ICOS ligation recruits the p50alpha PI3K regulatory subunit to the immunological synapse.
A secreted protein microarray platform for extracellular protein interaction discovery.
Proinflammatory stimuli induce galectin-9 in human mesenchymal stromal cells to suppress T-cell proliferation.
Soluble CD80 restores T cell activation and overcomes tumor cell programmed death ligand 1-mediated immune suppression.
A Human IgSF Cell-Surface Interactome Reveals a Complex Network of Protein-Protein Interactions.
-
Systematic interactome identified CD28-CD80 and CD28-CD86 interactions
"Cell-surface protein-protein interactions (PPIs) mediate cell-cell communication, recognition, and responses"
Structural characterization of a dimerization interface in the CD28 transmembrane domain.
-
NMR structure of CD28 TM domain confirming dimerization
"we determined the dimeric helix-helix packing of CD28-TMH using nuclear magnetic resonance (NMR) technology"
-
GxxxA motif mediates TM helix dimerization
"a GxxxA motif, which is highly conserved in many dimeric assemblies, is located at the dimerization interface"
-
Mutations in dimerization interface reduce IL-2 release
"Mutating G160 and A164 can disrupt the transmembrane helix assembly and reduces CD28 enhancement in cells"
A physical wiring diagram for the human immune system.
-
Systematic mapping of immune cell surface interactions including CD28-CD80 and CD28-CD86
"using a high-throughput surface receptor screening method, we systematically mapped the direct protein interactions across a recombinant library that encompasses most of the surface proteins that are detectable on human leukocytes"
Costimulation of CD4+ T cells via CD28 modulates human immunodeficiency virus type 1 infection and replication in vitro.
T-cell antigen CD28 interacts with the lipid kinase phosphatidylinositol 3-kinase by a cytoplasmic Tyr(P)-Met-Xaa-Met motif.
Binding of phosphatidylinositol-3-OH kinase to CD28 is required for T-cell signalling.
The regulation of protein synthesis and translation factors by CD3 and CD28 in human primary T lymphocytes.
Co-stimulation by CD28 (Reactome pathway)
-
Comprehensive pathway covering CD28 signaling including PI3K, Vav1, Grb2, Gads recruitment
"CD28 signaling plays a critical role in shaping immune responses by ensuring effective T-cell activation and enhancing T-cell survival and proliferation"
Nef mediated downregulation of CD28 cell surface expression
PI3K phosphorylation of PIP2 to PIP3 in CD28 signaling
PI3K inhibitors in CD28 signaling
CD28-bound PI3K phosphorylation of PIP2 to PIP3
Activation of Rac1 by pVav1 in CD28 pathway
Activation of Cdc42 by pVav1 in CD28 pathway
Translocation of Vav1 to CD28
Activation of Vav1 in CD28 pathway
Formation of Nef-CD28 cytoplasmic tail complex
Formation of Nef-CD28-Clathrin-Coated Pit Adapter Protein complex
Internalization of Nef-CD28-Clathrin complex
CD28 homodimer binding B7-2 monomer
CD28 homodimer binding B7-1 homodimer
Deep research review of CD28 biology (2024 literature synthesis)
-
Comprehensive review synthesizing 2024 literature on CD28 signaling, structure, and translational applications
-
YMNM/PRRP/PYAP motifs recruit PI3K/GRB2, ITK/PLCgamma1, and Lck/PKCtheta
-
CD28 costimulation accelerates Lck recruitment and ZAP70 activation at TCR microclusters