CD8 alpha

Function

Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primarily as a coreceptor for MHC class I molecule:peptide complex. The antigens presented by class I peptides are derived from cytosolic proteins while class II derived from extracellular proteins. Interacts simultaneously with the T-cell receptor (TCR) and the MHC class I proteins presented by antigen presenting cells (APCs). In turn, recruits the Src kinase LCK to the vicinity of the TCR-CD3 complex. LCK then initiates different intracellular signaling pathways by phosphorylating various substrates ultimately leading to lymphokine production, motility, adhesion and activation of cytotoxic T-lymphocytes (CTLs). This mechanism enables CTLs to recognize and eliminate infected cells and tumor cells. In NK-cells, the presence of CD8A homodimers at the cell surface provides a survival mechanism allowing conjugation and lysis of multiple target cells. CD8A homodimer molecules also promote the survival and differentiation of activated lymphocytes into memory CD8 T-cells.

Involvement in disease

Immunodeficiency 116

IMD116

An autosomal recessive immunologic defect characterized by absence of CD8+ cells, leading to recurrent bacterial infections.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

Palmitoylated, but association with CD8B seems to be more important for the enrichment of CD8A in lipid rafts.

O-glycosylated.

Phosphorylated in cytotoxic T-lymphocytes (CTLs) following activation.

Tissue specificity

CD8 on thymus-derived T-cells usually consists of a disulfide-linked alpha/CD8A and a beta/CD8B chain. Less frequently, CD8 can be expressed as a CD8A homodimer. A subset of natural killer cells, memory T-cells, intraepithelial lymphocytes, monocytes and dendritic cells expresses CD8A homodimers. Expressed at the cell surface of plasmacytoid dendritic cells upon herpes simplex virus-1 stimulation.

Cellular localization

• Isoform 1
• Cell membrane
• Single-pass type I membrane protein
• CD8A localizes to lipid rafts only when associated with its partner CD8B.
• Isoform 2
• Secreted

Alternative names

• MAL
• CD8A
• MAL
• T-cell surface glycoprotein CD8 alpha chain
• T-lymphocyte differentiation antigen T8/Leu-2

Database links

• entrezGene:940
• entrezGene:952
• entrezGene:926
• entrezGene:925
• omim:107270
• omim:186730
• omim:186760
• omim:186910
• swissprot:P01732
• swissprot:P28907
• swissprot:P10747
• swissprot:P10966

Target type

Proteins

Primary research area

Immuno-oncology

Other research areas

• Immunology & Infectious Disease

Molecular weight

25729Da