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.