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.
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We thank Simon Lee (IBMC) and Simon Davis (University of Oxford) for reviewing the manuscript. This work was supported by the European Regional Development Fund (FEDER) through Programa Operacional Factores de Competitividade – COMPETE, and by the Portuguese Government through FCT – Fundação para a Ciência e a Tecnologia, projects PTDC/SAU-MII/98041/2008 and PEst-C/SAU/LA0002/2011. M.P. is funded by Programa Ciência 2007 (FCT). The authors have no conflict of interest.
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Pinto, M., Carmo, A.M. CD6 as a Therapeutic Target in Autoimmune Diseases: Successes and Challenges. BioDrugs 27, 191–202 (2013). https://doi.org/10.1007/s40259-013-0027-4
- Experimental Autoimmune Encephalomyelitis
- Activate Leukocyte Cell Adhesion Molecule
- Bone Marrow Graft
- Immune Synapse
- SRCR Domain