Title:Tuning T Cell Activation: The Function of CD6 At the Immunological Synapse and in T Cell Responses
Volume: 17
Issue: 6
Author(s): Rita F. Santos, Liliana Oliveira and Alexandre M. Carmo
Affiliation:
Keywords:
CD6, immunological synapse, T lymphocyte activation, inhibitory receptors, alternative splicing, immunotherapy.
Abstract: CD6 immunotherapy to treat psoriasis and rheumatoid arthritis has reached the clinical trial
stage with apparent success, and targeting CD6 with mAbs is being used in several animal models of
autoimmunity and neuroinflammation with promising indications. However, the mode of action of the
therapeutic CD6 mAbs is far from being understood, reflecting the uncertainties and controversy surrounding
the mechanistic and biological functions of CD6. Initially regarded as a co-stimulatory receptor
of T lymphocytes, recent studies suggest that CD6 can instead modulate early as well as late T cell
responses. Also, opposing the contribution of CD6 adhesiveness in the establishment and stabilization of immunological
synapses, the actual triggering of CD6 might induce anti-proliferative signals to the T lymphocyte. CD6 has an unusually
long cytoplasmic tail and its gene undergoes peculiar patterns of activation-dependent alternative splicing that can on one
hand determine whether or not the CD6 protein binds to its ligand, and on the other include or exclude intracellular sequences
that may transduce positive or negative signaling. In this review we discuss the multiple aspects that determine
the nature of the signals transmitted via CD6 and the context that may define a dual role for this important T cell surface
molecule.