CD8: adhesion molecule, co-receptor and immuno-modulator

Abstract

CD8 is a cell surface glycoprotein found in cytotoxic T lymphocytes, which are important components in cellular immunity, esp. in the immune response to cancer and chronic infections. There are two forms of CD8, either as an alphaalpha homodimer or alphabeta heterodimer. It acts as an "assistant" or co-receptor in the function of cytotoxic T cells where specific immunity is mediated by interaction of specific T cell receptor (alphabeta TCR) and its ligand peptide major histocompatibility complex (pMHC). CD8 also binds to pMHC but away from the interface of pMHC and TCR contact, thereof no influence on the specificity of this interaction. If the TCR and CD8 bind to the same pMHC at the same time, CD8 is defined as a co-receptor, functioning through its signalling via its cytoplasmic tyrosine phosphorylation pathway; if CD8 binds to pMHC independently of the TCR, it is defined as an adhesion molecule. At present, the co-receptor function theory is dominated in the field. Recent study has also shown that murine CD8 alphaalpha binds to TL antigen, an MHC homologue, therefore acts as an immuno-modulator. In this review, we discuss these current understandings of the three aspects of the CD8 functions and their structural basis.