CD8A Gene: Function, Expression, and Clinical Significance

The CD8A gene encodes the CD8 alpha chain, a transmembrane glycoprotein that forms heterodimers with CD8 beta (CD8B) on the surface of cytotoxic T lymphocytes (CTLs) and thymocytes. CD8 acts as a co-receptor for the T cell receptor (TCR), binding to major histocompatibility complex class I (MHC-I) molecules on antigen-presenting cells. This interaction stabilizes the TCR-antigen-MHC complex and recruits the intracellular tyrosine kinase LCK, which is essential for T cell activation and effector function. CD8A is also expressed on a subset of natural killer (NK) cells and dendritic cells. Mutations in CD8A can lead to CD8 deficiency, an immunodeficiency characterized by recurrent infections and impaired cytotoxic T cell responses.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• T cell receptor signaling pathway

• PD-1 signaling

• Costimulation by the CD28 family

• Antigen processing and presentation

• Cytokine-cytokine receptor interaction

The CD8 alpha chain (UniProt P01732) is a 235-amino acid type I membrane protein with an extracellular immunoglobulin-like domain, a transmembrane region, and a cytoplasmic tail containing a CXCP motif that binds LCK. It forms a disulfide-linked heterodimer with CD8 beta (P10966) on the cell surface. The extracellular domain interacts with the alpha3 domain of MHC class I molecules, while the cytoplasmic tail recruits LCK to phosphorylate TCR-associated CD3 chains, initiating downstream signaling cascades. CD8 is critical for positive selection of thymocytes and for cytotoxic T cell effector functions, including cytokine production and target cell killing.