CD8

CD8 is a transmembrane glycoprotein that functions as a co-receptor on most cytotoxic T lymphocytes (CD8+ T cells). It exists mainly as a heterodimer composed of CD8 alpha and CD8 beta chains (CD8αβ), though some T cells express CD8αα homodimers. The CD8 molecule binds to conserved regions of MHC class I molecules on nucleated cells, while the T cell receptor (TCR) recognizes the peptide presented by MHC I. By engaging MHC I, CD8 stabilizes the TCR–peptide–MHC complex and helps recruit the Src family kinase Lck to the TCR complex, amplifying signaling for T cell activation. The CD8A and CD8B genes encode the alpha and beta chains, located in the MHC region on chromosome 2 in humans.

CD8+ T cells act as cytotoxic effector cells in adaptive immunity. Upon recognition of antigen presented by MHC class I on infected or transformed cells, they release cytotoxic granules containing perforin and granzymes and can also trigger apoptosis through Fas-FasL interactions or cytokine production. CD8+ T cells differentiate in the thymus and in peripheral tissues into various subsets, including naive, effector, and memory cells that contribute to long-term immunity. CD8 expression serves as a key phenotypic marker distinguishing cytotoxic T cells from CD4+ helper T cells, which mostly recognize peptides presented by MHC class II.

Clinical relevance: In laboratory analysis, CD8 is used as a marker to identify cytotoxic T cells by flow cytometry. CD8+ T cell numbers and function are important in infections, cancers, and immunodeficiencies. In HIV infection, CD8+ T cells contribute to control of viral replication. In cancer immunotherapy, CD8+ T cells are central to approaches such as adoptive T cell transfer and CAR-T cell therapy, where cytotoxic T cells are employed to target tumor cells.