Peptide blockers of Kv1.3 channels in T cells as therapeutics for autoimmune disease

The voltage-gated K(v)1.3 channel in T lymphocytes is a validated therapeutic target for diverse autoimmune diseases. Here we review the discovery of K(v)1.3, its physiological role in T cells, and why it is an attractive target for modulating autoimmune responses. We focus on peptide inhibitors because the first K(v)1.3-selective inhibitor in human trials is a peptide derived from a marine organism. Two broad classes of peptides block K(v)1.3, the first from scorpions and the second from sea anemones. We describe their structures, their binding site in the external vestibule of K(v)1.3, how they have been engineered to improve K(v)1.3-specificity, and their pharmacokinetic and pharmacodynamic properties. Finally, we highlight the therapeutic potential of K(v)1.3 peptide inhibitors to treat autoimmune diseases without compromising protective immune responses.