title: CD6 as a therapeutic target in autoimmune diseases: successes and challenges.
abstract: The transmembrane surface glycoprotein CD6 was one of the first antigens identified on T lymphocytes. The recognition of its involvement in T-cell signaling processes heralds the potential of CD6 as a target for therapy in a number of pathologies associated with imbalances in T-cell function. Its tissue distribution, cellular expression, and overall molecular structure are well described, and the interaction with its physiological ligand CD166 has been determined to the amino-acid level. Nevertheless, the involvement of CD6 in signaling pathways remains poorly characterized and its biological function is controversial; still unresolved are whether CD6 is a co-stimulatory molecule in T-cell activation or, similar to the related CD5 antigen, a modulator of intracellular signaling. Here we revisit the earliest attempts of modulating immune function using CD6 monoclonal antibodies, and review the current thinking behind the recent developments in immunotherapy targeting CD6. Notwithstanding the promises and hopes brought by monoclonals already in clinical trials, the fact is that very little is known about the mechanism of action of these reagents, whether they enhance the physiological role of the receptor or whether they may induce a completely novel biochemical response that might, nevertheless, be beneficially used to treat human immune pathology.
authors.affiliation: Cell Activation and Gene Expression Group, IBMC - Instituto de Biologia Molecular e Celular, Rua do Campo Alegre 823, 4150-180, Porto, Portugal.
authors.forename: Mafalda
authors.initials: M
authors.lastname: Pinto
authors.forename: Alexandre M
authors.initials: AM
authors.lastname: Carmo
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism / Q000627:therapeutic use*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology* / Q000627:therapeutic use*; D001327:Autoimmune Diseases / Q000276:immunology* / Q000628:therapy*; D018956:CD5 Antigens / Q000276:immunology / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D049109:Cell Proliferation; D005326:Fetal Proteins / Q000378:metabolism; D006801:Humans; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D020410:Activated-Leukocyte Cell Adhesion Molecule
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018956:CD5 Antigens; D015816:Cell Adhesion Molecules, Neuronal; D005326:Fetal Proteins; C105613:ALCAM protein, human; D020410:Activated-Leukocyte Cell Adhesion Molecule; C062279:CD6 antigen