This FIRST proposal explores the role of the C-C' loop, HWKNSNQIKILG in CD4 interactions as a recognition element in CD4+ T cell interactions. Autoimmune diseases impose a great burden on society and the families of the patients, so the subject of the proposed studies is well justified. The best therapeutic target for the disease has still not been identified, and peptides and peptidomimetics are often considered possible curative candidates. The preliminary results are quite encouraging with a cyclic hexapeptide CNSNQIC showing at least 50 percent inhibition of responder cell alloreactive proliferation as well as amelioration of the severity of an experimental encephelitis model in mice when given once. The NMR of this cyclic peptide in DMSO is consistent with a type I b-turn conformation similar to that seen in the crystal structure of CD4. A labelled analog of the cyclic hexapeptide has also been prepared for binding studies.
