New conformationally restricted analog of the immunosuppressory mini-domain of HLA-DQ and its biological properties

Our previous studies revealed that the nonapeptide fragment of HLA-DQ locat ed in the beta 164-172 loop of the Thr-Pro-Gln-Arg-Gly-Asp-Val-Tyr-Thr sequ ence suppresses the immune humoral and cellular responses [30]. Based on th e crystal structure of HLA-class Il molecules we designed and synthesized a cyclic analog with restricted conformation, cyclo(Suc-Thr-Pro-Gln-Arg-Gly- Asp-Val-Lys)-Thr-OH (Suc = succinyl) by reacting a Lys side chain with a su ccinylated N-terminus. The cyclization product more potently suppresses the cellular immune response than its linear counterparts and is efficiently c leaved by trypsin. The results indicate that the beta 164-172 loop may serv e as a functional epitope on the HLA class II surface for intermolecular bi nding. (C) 2000 Published by Elsevier Science Inc.