The immunosuppressory and adhesive miniregion of the human major histocompatibility protein, human leukocyte antigen DQ.
Our previous studies showed that the nonapeptide fragment of human leukocyte antigen DQ with the TPQRGDVYT sequence strongly suppresses the immune response [Z. Szewczuk, I. Z. Siemion, and Z. Wieczorek (1996) Molecular Immunology, 33, 903-9081]. The fragment contains the RGDVY sequence, which is very similar to thymopentin (pentapeptide RKDVY, an active fragment (32-36) of thymopoietin, an immune system activator produced in thymi), and at the same time contains the RGD sequence, known as an inhibitor of adhesion processes. In the present study we tested an influence of the nonapeptide and its shorter fragments on binding the activated platelets and K562 cells to fibrinogen and fibronectin, respectively. We also designed and synthesized a cyclic thymopentin-like peptide. C*RGDVYC* (where C* indicates Cys participating in disulfide bridge) to restrict its conformation. The cyclization product strongly suppresses the humoral and cellular immune response and selectively inhibits the adhesion of K562 cells to fibronectin. The results are discussed in the light of CD conformational studies.
Szewczuk
Z
Z
Department of Chemistry, University of Wroclaw, Poland.
Stefanowicz
P
P
Wilczyński
A
A
Siemion
I Z
IZ
Cierniewski
C S
CS
Kralisz
U
U
Wieczorek
Z
Z
D000818:Animals; D001665:Binding Sites; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects*; D002942:Circular Dichroism; D006683:HLA-DQ Antigens / Q000737:chemistry*; D006462:Hemolytic Plaque Technique; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007166:Immunosuppressive Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008958:Models, Molecular; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010973:Platelet Adhesiveness / Q000187:drug effects*; D011487:Protein Conformation; D014407:Tumor Cells, Cultured
D006683:HLA-DQ Antigens; D007166:Immunosuppressive Agents; D010446:Peptide Fragments; D010456:Peptides, Cyclic