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人类主要组织相容性蛋白——人类白细胞抗原DQ的免疫抑制及黏附微区

The immunosuppressory and adhesive miniregion of the human major histocompatibility protein, human leukocyte antigen DQ.

作者信息

Szewczuk Z, Stefanowicz P, Wilczyński A, Siemion I Z, Cierniewski C S, Kralisz U, Wieczorek Z

机构信息

Department of Chemistry, University of Wroclaw, Poland.

出版信息

Biopolymers. 1996;40(5):571-83. doi: 10.1002/(SICI)1097-0282(1996)40:5%3C571::AID-BIP15%3E3.0.CO;2-K.

DOI:10.1002/(SICI)1097-0282(1996)40:5%3C571::AID-BIP15%3E3.0.CO;2-K
PMID:9062075
Abstract

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. CRGDVYC (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.

摘要

我们之前的研究表明,具有TPQRGDVYT序列的人白细胞抗原DQ九肽片段能强烈抑制免疫反应[Z. 谢夫祖克、I. Z. 谢米昂和Z. 维乔雷克(1996年),《分子免疫学》,第33卷,903 - 908页]。该片段包含RGDVY序列,它与胸腺五肽(五肽RKDVY,胸腺生成素的活性片段(32 - 36),一种在胸腺中产生的免疫系统激活剂)非常相似,同时还包含RGD序列,该序列是已知的黏附过程抑制剂。在本研究中,我们测试了九肽及其较短片段分别对活化血小板与纤维蛋白原以及K562细胞与纤连蛋白结合的影响。我们还设计并合成了一种环状胸腺五肽样肽CRGDVYC(其中C*表示参与二硫键形成的半胱氨酸)以限制其构象。该环化产物能强烈抑制体液免疫和细胞免疫反应,并选择性地抑制K562细胞与纤连蛋白的黏附。根据CD构象研究对结果进行了讨论。

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