CD58 (LFA-3): A Key Immune Adhesion Molecule in T-Cell Activation and Cancer Immune Evasion
Explore the CD58 gene, its role in immune synapse formation, its implications in hematological malignancies, and its potential as a therapeutic target.
Gene Information Card
| Symbol | CD58 |
|---|---|
| Full Name | CD58 molecule (LFA-3) |
| Gene Type | Protein coding |
| Chromosomal Location | 1p13.1 |
| NCBI Gene ID | 965 ncbi.nlm.nih.gov/gene/965 |
| Ensembl ID | ENSG00000116815 |
| UniProt ID | P19256 |
| OMIM ID | 153420 |
| HGNC ID | 1688 |
| Aliases | LFA-3, LFA3, CD58 antigen, ag3, surface glycoprotein LFA-3 |
Description
The CD58 gene encodes the CD58 protein, also known as Lymphocyte Function-Associated Antigen-3 (LFA-3). This cell surface glycoprotein is a member of the immunoglobulin superfamily and is widely expressed on various cell types, including antigen-presenting cells (APCs), endothelial cells, and fibroblasts. CD58 functions as a ligand for the CD2 receptor found on T cells and natural killer (NK) cells. The interaction between CD58 and CD2 is crucial for the formation of the immunological synapse, enhancing T-cell activation, cytokine production, and NK cell-mediated cytotoxicity. In the context of cancer, particularly hematological malignancies like diffuse large B-cell lymphoma (DLBCL), CD58 expression is often downregulated or mutated, allowing tumor cells to evade immune surveillance. This makes CD58 a critical molecule in both normal immune function and cancer pathogenesis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Diffuse Large B-Cell Lymphoma (DLBCL) | Somatic mutations and deletions of the CD58 gene lead to loss of CD58 protein expression on tumor cells. This prevents CD2-mediated activation of T cells and NK cells, allowing the lymphoma cells to escape immune destruction. | Multiple studies, including genomic analyses from the NCBI and COSMIC databases, have identified CD58 as a recurrently mutated gene in DLBCL, with mutations found in approximately 10-20% of cases. Loss of CD58 expression is associated with a poorer prognosis. |
| Multiple Sclerosis (MS) | Genetic variations (single nucleotide polymorphisms, SNPs) in the CD58 gene have been associated with susceptibility to multiple sclerosis. The risk-associated allele is thought to lead to increased CD58 expression on immune cells, potentially enhancing regulatory T-cell function and modulating the autoimmune response. | Genome-wide association studies (GWAS) have consistently linked the CD58 locus to MS risk. Functional studies suggest that the protective allele is associated with higher CD58 expression, which may enhance the suppressive capacity of regulatory T cells. |
| Rheumatoid Arthritis (RA) | Similar to MS, genetic variants in the CD58 gene have been implicated in the susceptibility to rheumatoid arthritis. The exact mechanism is still under investigation, but it is likely related to the role of CD58 in T-cell co-stimulation and the regulation of inflammatory responses. | GWAS studies have identified CD58 as a risk locus for RA, highlighting its broader role in autoimmune diseases. |
| Immunodeficiency | While rare, homozygous loss-of-function mutations in CD58 can lead to a primary immunodeficiency characterized by recurrent infections, particularly with viruses. The lack of CD58 impairs the ability of T cells and NK cells to effectively interact with and clear infected cells. | Case reports and functional studies have demonstrated that CD58 deficiency results in defective T-cell and NK-cell cytotoxicity, leading to severe viral infections. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Blood | ~50 | High |
| Spleen | ~40 | High |
| Lymph Node | ~35 | High |
| Bone Marrow | ~30 | Medium |
| Lung | ~25 | Medium |
| Skin | ~20 | Medium |
| Liver | ~15 | Low |
| Brain | ~5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Raji (Burkitt's Lymphoma) | ~60 | High expression, often used as a positive control in flow cytometry. |
| K-562 (Chronic Myelogenous Leukemia) | ~10 | Low expression, representing a model for NK cell evasion. |
| HeLa (Cervical Carcinoma) | ~25 | Moderate expression, typical of non-hematopoietic cells. |
| Jurkat (T-cell Leukemia) | ~5 | Low expression, as T cells primarily express the receptor CD2, not the ligand CD58. |
| THP-1 (Monocytic Leukemia) | ~45 | High expression, consistent with its role as an antigen-presenting cell line. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1Val) | Missense | Rare (<1%) | Disrupts the start codon, likely leading to a non-functional protein or no protein expression. |
| c.250C>T (p.Arg84Ter) | Nonsense | Rare (<1%) | Introduces a premature stop codon, resulting in a truncated, non-functional protein. |
| c.400_401insA (p.Leu134fs) | Frameshift | Rare (<1%) | Causes a frameshift in the coding sequence, leading to a truncated protein and loss of function. |
| c.550G>A (p.Gly184Arg) | Missense | Rare (<1%) | A missense mutation in the extracellular domain that may affect protein folding or binding to CD2. |
| Whole Gene Deletion | Copy Number Loss | ~10-20% in DLBCL | Homozygous or hemizygous deletion of the CD58 locus results in complete loss of CD58 expression on the cell surface. |
Mutation functional classification
Loss of Function (LOF)
The most common mechanism in cancer. Mutations, deletions, or promoter hypermethylation lead to reduced or absent CD58 expression on tumor cells. This allows tumors to evade CD2-mediated immune surveillance by T cells and NK cells.
Gain of Function (GOF)
Not a common mechanism for CD58 in disease. However, in some autoimmune contexts, genetic variants that increase CD58 expression are considered 'gain-of-function' and may contribute to enhanced regulatory T-cell activity.
Dominant Negative (DN)
Not a well-documented mechanism for CD58. Since CD58 functions as a cell surface ligand, a mutant protein is unlikely to exert a dominant-negative effect over the wild-type protein in a heterozygous state, as the loss of one allele is often sufficient to reduce ligand density below a functional threshold.
View complete mutation data：
Gene Ontology (GO)
| • protein binding | • receptor ligand activity |
| • cell adhesion molecule binding | • plasma membrane |
| • external side of plasma membrane | • cell surface |
| • cell-cell adhesion | • T cell costimulation |
| • immune response | • cell recognition |
| • positive regulation of T cell activation | • natural killer cell mediated cytotoxicity |
Pathways
• T cell receptor signaling pathway
• Natural killer cell mediated cytotoxicity
• Cell adhesion molecules (CAMs)
• Immune System
• Adaptive Immune System
Protein Summary
The CD58 protein, also known as LFA-3, is a heavily glycosylated type I transmembrane protein. It consists of two N-terminal immunoglobulin-like domains (a V-like and a C2-like domain) in its extracellular region, a transmembrane domain, and a short cytoplasmic tail. The primary function of CD58 is to bind to the CD2 receptor on T cells and NK cells. This interaction is one of the key co-stimulatory signals required for efficient T-cell activation and NK cell cytotoxicity. CD58 is expressed on a wide variety of cells, including antigen-presenting cells, where it helps to stabilize the immunological synapse. In cancer, loss of CD58 expression is a common immune evasion mechanism, particularly in lymphomas. The protein is also a target for therapeutic antibodies and chimeric antigen receptor (CAR) T-cell therapies.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CD58 Knockout HEK293 Cell Line | EDJ-KQ4224 | Human | 965 | Details Get a Quote |
| CD58 Knockout HCT 116 Cell Line | EDJ-KQ25374 | Human | 965 | Details Get a Quote |
| CD58 Knockout A-549 Cell Line | EDJ-KQ26688 | Human | 965 | Details Get a Quote |
| CD58 Knockout HeLa Cell Line | EDJ-KQ26689 | Human | 965 | Details Get a Quote |
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