CD8A Gene

The CD8A gene (CD8A stands for Cluster of Differentiation 8a) is a protein coding gene located on chromosome 2p11.2. The protein encoded by the CD8A gene(CD8 antigen), CD8 alpha chain, is a cell surface glycoprotein found on cytotoxic T lymphocytes. It mediates efficient cell-cell interactions within the immune system. Here, the CD8 antigen functions as a co-receptor of the T cell receptor for recognition of antigens presented by an antigen-presenting cell in association with class I MHC molecules.

The CD8 protein functions either as a homodimer consisting of two alpha chains or as a heterodimer consisting of one alpha and one beta chain. Both the alpha and beta chains show significant homology to the variable light chains of immunoglobulins.

Several transcript variants encoding different isoforms have been found for the CD8A gene. The major protein isoforms of this gene differ by the presence or absence of a transmembrane domain resulting in the functional difference between the membrane-anchored or the secreted form. Associated signaling pathways include T cell receptor and co-stimulatory signaling as well as TCR signaling.

The CD8A -gene gene encodes the CD8 alpha chain integral membrane glycoprotein, which plays an essential role in the immune response and serves multiple functions in responding to external and internal attacks. In T cells, it functions primarily as a co-receptor for the MHC class I molecule-peptide complex. The antigens presented by class I peptides originate from cytosolic proteins, whereas class II originates from extracellular proteins.

The CD8 protein simultaneously interacts with the T cell receptor (TCR) and 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. This kinase then initiates various intracellular signaling pathways by phosphorylating different substrates, which eventually leads to the production of lymphokines, motility, adhesion, and activation of cytotoxic T lymphocytes (CTL). This mechanism enables CTLs to recognize and eliminate infected cells and tumor cells. In NK cells, the presence of CD8A homodimers on the cell surface provides a survival mechanism that enables conjugation and lysis of multiple target cells. CD8A homodimer molecules also promote the survival and differentiation of activated lymphocytes into memory CD8 T cells.

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