Peptide blockers of K1.3 channels in T cells as therapeutics for autoimmune disease.

The voltage-gated K1.3 channel in T lymphocytes is a validated therapeutic target for diverse autoimmune diseases. Here we review the discovery of K1.3, 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 K1.3-selective inhibitor in human trials is a peptide derived from a marine organism. Two broad classes of peptides block K1.3, the first from scorpions and the second from sea anemones. We describe their structures, their binding site in the external vestibule of K1.3, how they have been engineered to improve K1.3-specificity, and their pharmacokinetic and pharmacodynamic properties. Finally, we highlight the therapeutic potential of K1.3 peptide inhibitors to treat autoimmune diseases without compromising protective immune responses.