CD6 as a Cell Surface Receptor and As a Target for Regulating Immune Responses

CD6 has been exploited as a drug target as its expression is restricted, primarily to T cells, it has a well characterised cell surface ligand, CD166 and regulates T cell activation through a long cytoplasmic tail. CD6 can affect both the initiation and maintenance of T cell function in a negative and positive manner respectively so that it is important to understand these dual effects of a potential drug target. The effective mode of action of clinical monoclonal antibodies (mAbs) that recognise cell surface receptors including CD6 is commonly cytotoxic depletion of cells. It is not clear how current therapeutic strategies to target CD6 perturb function. With the benefit of new structural data, this review provides a critical analysis and interpretation of experiments in which various reagents have been tested and offers some suggestions as how more effective drugs may be developed.