coreceptor

A coreceptor is a cell-surface molecule that forms part of a receptor complex and is required to achieve full activation or entry by a ligand or pathogen. Coreceptors themselves do not typically bind the ligand strongly enough to signal alone, but they stabilize the interaction with the primary receptor and/or initiate signaling pathways together with it.

In adaptive immunity, T cells express co-receptors CD4 and CD8 that bind to MHC class II and I, respectively, increasing the affinity of the TCR for peptide-MHC and recruiting protein tyrosine kinases such as Lck to the immunological synapse, lowering the threshold for activation.

Many pathogens exploit coreceptors to enter cells. For HIV, the primary receptor is CD4, while the chemokine receptors CCR5 (R5-tropic viruses) or CXCR4 (X4-tropic) serve as coreceptors necessary for viral fusion and entry. Individuals with homozygous CCR5-Δ32 mutation show resistance to certain HIV strains. Chemokine receptors are typical coreceptors and are G protein-coupled receptors.

Coreceptors may also influence cell signaling and trafficking by modulating receptor conformation and downstream signaling cascades. They are targets for drugs, such as CCR5 antagonists used in HIV therapy, and research explores coreceptors in other diseases and in cancer metastasis.