Immunosuppressory mini-regions of HLA-DP and HLA-DR

Our previous studies showed, that the TPQRGDVYT, QRGDVYT and RGDVYT fragmen ts, located in the beta 164-172 loop of HLA-DQ, strongly suppress the humor al and cellular immune response, while their shorter analogs, RGDV, RGDVY, and QRGDVY, show only weak stimulatory activity in respect to humoral immun ological response. The fragments contain the RGDVY sequence that is analogo us to thymopentin (pentapeptide RKDVY, an immune system activator) as well as the RGD sequence, known for its importance for cellular association phen omena. Based on the crystal structure of HLA-DR1, we also designed and synt hesized a cyclic analog C*RGDVYC* (where C* indicates Cys participating in disulfide bridge) with restricted conformation, which strongly suppresses b oth humoral and cellular immune response. In the present study we synthesiz ed and tested the immunological properties of the linear and cyclic HLA-DP and HLA-DR counterparts of all the above HLA-DQ fragments. Although the res ults show that the linear HLA-DP fragments possess moderate immunosuppresso ry potency, their conformationally restricted analog, C*QGDVYC*C shows a co nsiderable suppression of both humoral and cellular immune response. The no napeptide fragment of HLA-DR, VPRSGEVYT and particularly its cyclic analog C*SGEVYC*, are strong suppressors of the humoral response. (C) 1999 Elsevie r Science Ltd. All rights reserved.