CD28 Gene - Costimulatory Receptor in T Cell Activation
A critical immune checkpoint receptor encoded by the CD28 gene, essential for T cell activation, proliferation, and survival, with implications in autoimmunity, cancer immunotherapy, and primary immunodeficiency.
Gene Information Card
| Symbol | CD28 |
|---|---|
| Full Name | CD28 molecule |
| Gene Type | protein coding |
| Chromosomal Location | 2q33.2 |
| NCBI Gene ID | 940 ncbi.nlm.nih.gov/gene/940 |
| Ensembl ID | ENSG00000178568 |
| UniProt ID | P10747 |
| OMIM ID | 186760 |
| HGNC ID | 1653 |
| Aliases | Tp44, T-cell-specific surface glycoprotein CD28 |
Description
The CD28 gene encodes a type I transmembrane glycoprotein that is a member of the immunoglobulin superfamily. It is constitutively expressed on the surface of most T cells and provides a crucial costimulatory signal required for optimal T cell activation and survival. CD28 binds to B7-1 (CD80) and B7-2 (CD86) on antigen-presenting cells, delivering a signal that synergizes with T cell receptor (TCR) engagement to promote IL-2 production, T cell proliferation, and differentiation. CD28 also plays a role in T cell memory and homeostasis. Its signaling is modulated by CTLA-4, a competitive inhibitor, and dysregulation of CD28 is implicated in various immune-mediated diseases and cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Primary immunodeficiency (CD28 deficiency) | Loss-of-function mutations impair T cell costimulation, leading to reduced T cell activation and antibody responses. | OMIM #186760; case reports in ClinVar |
| Autoimmune diseases (e.g., rheumatoid arthritis, type 1 diabetes) | Polymorphisms in CD28 gene may alter costimulatory signaling, contributing to aberrant T cell responses. | GWAS studies; NCBI Gene |
| Cancer (immunotherapy response) | CD28 expression on T cells is essential for checkpoint inhibitor efficacy; loss of CD28 can lead to T cell exhaustion and resistance. | COSMIC and literature |
| Lymphoproliferative disorders | Somatic mutations in CD28 have been identified in some T cell lymphomas, potentially driving oncogenic signaling. | COSMIC database |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | High (nTPM ~ 200) | High |
| Spleen | High (nTPM ~ 180) | High |
| Blood | High (nTPM ~ 150) | High |
| Bone marrow | Moderate (nTPM ~ 50) | Moderate |
| Thymus | Moderate (nTPM ~ 40) | Moderate |
| Lung | Low (nTPM ~ 10) | Low |
| Liver | Low (nTPM ~ 5) | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Jurkat (T cell leukemia) | High (nTPM ~ 300) | T cell line; CD28 highly expressed |
| Ramos (B cell lymphoma) | Low (nTPM ~ 5) | B cell line; minimal expression |
| K562 (chronic myelogenous leukemia) | Low (nTPM ~ 2) | Non-T cell line; minimal expression |
| MCF7 (breast cancer) | Low (nTPM ~ 1) | Epithelial line; no significant expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.137A>G (p.Tyr46Cys) | Missense | Rare | Impairs CD28 ligand binding, leading to reduced costimulation |
| c.412C>T (p.Arg138Trp) | Missense | Rare | Disrupts signaling domain, affecting T cell activation |
| c.562+1G>A | Splice site | Rare | Causes exon skipping, leading to truncated protein |
| c.623A>G (p.Asn208Ser) | Missense | Somatic in lymphoma | Potential gain-of-function, enhancing survival signals |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in CD28, such as missense variants affecting ligand binding or signaling, result in impaired T cell costimulation, leading to immunodeficiency and increased susceptibility to infections.
Gain of Function (GOF)
Gain-of-function mutations, often somatic in T cell lymphomas, may enhance CD28 signaling, promoting T cell proliferation and survival, contributing to oncogenesis.
Dominant Negative (DN)
Dominant-negative mutations are rare but could interfere with wild-type CD28 function by forming non-functional dimers or competing for ligands, thereby suppressing T cell responses.
View complete mutation data：
Gene Ontology (GO)
| • receptor activity (GO:0004872) | • protein binding (GO:0005515) |
| • signal transduction (GO:0007165) | • adaptive immune response (GO:0002250) |
| • T cell activation (GO:0042110) | • plasma membrane (GO:0005886) |
Pathways
• T cell receptor signaling pathway (KEGG hsa04660)
• Costimulation by the CD28 family (Reactome R-HSA-388841)
• PD-1 signaling (Reactome R-HSA-389948)
• Immune checkpoint pathway (WikiPathways WP4410)
Protein Summary
The CD28 protein is a 220-amino acid type I transmembrane glycoprotein with a single extracellular immunoglobulin V-like domain, a transmembrane region, and a cytoplasmic tail containing YMNM and PYAP motifs. It forms homodimers on the T cell surface. Upon binding to CD80/CD86, CD28 recruits PI3K and GRB2, activating downstream pathways such as PI3K-AKT and MAPK, which promote IL-2 transcription and T cell survival. CD28 also interacts with CTLA-4, which has higher affinity for B7 ligands and mediates inhibitory signals. The protein is essential for T cell-dependent immune responses and is a target for therapeutic modulation in autoimmunity and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CD28 Knockout HEK293 Cell Line | EDJ-KQ17742 | Human | 940 | Details Get a Quote |
| CD28 Knockout HeLa Cell Line | EDJ-KQ52828 | Human | 940 | Details Get a Quote |
| CD28 Knockout A-549 Cell Line | EDJ-KQ61298 | Human | 940 | Details Get a Quote |
| CD28 Knockout HCT 116 Cell Line | EDJ-KQ69793 | Human | 940 | Details Get a Quote |
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