The two main immunosuppressant drugs used today, cyclosporin A and FK506, prevent the rejection of foreign organs or bone marrow by disrupting the signaling pathway that activates T cells. But both drugs can cause kidney and nervous system damage, making them unsuitable for wider clinical application. The newly identified peptide prevents a single, specific step in the immune system's signaling pathway, so researchers anticipate that it will not cause serious side effects.
Anjana Rao, professor of pathology, Patrick Hogan, investigator, and their colleagues at Harvard Medical School and the Center for Blood Research made a peptide that binds to calcineurin, a key molecule in the pathway that transmits signals from the T cell receptor to the nucleus. The key difference between how the peptide and the drugs cyclosporin A and FK506 work is the region on calcineurin where each of these agents bind. Cyclosporin A and FK506 block the active site of calcineurin and prevent it from acting on any other molecules within the cell. The peptide, on the other hand, only blocks specific binding between calcineurin and NFAT (nuclear factor of activated T cells). Other calcineurin functions are unimpeded.
With the peptide in place, calcineurin is unable to bind to the
transcription factor NFAT and the signaling pa
Contact: Peta Gillyatt
Harvard Medical School