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人类巨细胞病毒与HLA - DRβ链的序列同源性和免疫交叉反应性:移植排斥和免疫抑制的一种机制

Sequence homology and immunologic cross-reactivity of human cytomegalovirus with HLA-DR beta chain: a means for graft rejection and immunosuppression.

作者信息

Fujinami R S, Nelson J A, Walker L, Oldstone M B

机构信息

Department of Pathology, University of California, San Diego, La Jolla 92093.

出版信息

J Virol. 1988 Jan;62(1):100-5. doi: 10.1128/JVI.62.1.100-105.1988.

DOI:10.1128/JVI.62.1.100-105.1988
PMID:2446012
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC250506/
Abstract

A peptide (Leu-Gly-Arg-Pro-Asp-Glu-Asp-Ser-Ser-Ser-Ser-Ser-Ser-Ser-Cys) that was identical to residues 82 through 96 of a predicted protein of 208 amino acids from the immediate-early region (IE-2) nucleic acid sequence of human cytomegalovirus was chemically synthesized. By computer analysis, the first five amino acids of this peptide showed sequence homology to the beta chain of the human histocompatibility complex HLA-DR. The homologous amino acids, 53 through 57, were located in a region that is conserved between the human DR beta chain and the beta chain of the H-2 class II histocompatibility antigen for mice. The shared region between the IE-2 protein and DR beta chain were similar in both hydrophilicity and predicted beta-turn potential. The IE-2 viral peptide induced antibodies that specifically recognized the human DR beta chain. These observations describe a protein encoded by the IE-2 region of human cytomegalovirus that contains sequence homology and shows immunologic cross-reactivity with a conserved domain of HLA-DR and suggest a mechanism to explain how human cytomegalovirus infection contributes to graft rejection after transplantation.

摘要

化学合成了一种肽(Leu-Gly-Arg-Pro-Asp-Glu-Asp-Ser-Ser-Ser-Ser-Ser-Ser-Ser-Cys),它与人巨细胞病毒即刻早期区域(IE-2)核酸序列预测的208个氨基酸的蛋白质的第82至96位残基相同。通过计算机分析,该肽的前五个氨基酸显示出与人组织相容性复合体HLA-DR的β链的序列同源性。同源氨基酸残基53至57位于人DRβ链与小鼠H-2Ⅱ类组织相容性抗原β链之间保守的区域。IE-2蛋白与DRβ链之间的共享区域在亲水性和预测的β-转角潜力方面都相似。IE-2病毒肽诱导出能特异性识别人类DRβ链的抗体。这些观察结果描述了一种由人巨细胞病毒IE-2区域编码的蛋白质,它与HLA-DR的一个保守结构域具有序列同源性并显示出免疫交叉反应性,并提示了一种机制来解释人巨细胞病毒感染如何导致移植后移植物排斥反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53de/250506/fb8d796dd2ea/jvirol00080-0123-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53de/250506/fb8d796dd2ea/jvirol00080-0123-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53de/250506/fb8d796dd2ea/jvirol00080-0123-a.jpg

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Complete amino acid sequence of an HLA-DR antigen-like beta chain as predicted from the nucleotide sequence: similarities with immunoglobulins and HLA-A, -B, and -C antigens.根据核苷酸序列预测的一种HLA - DR抗原样β链的完整氨基酸序列:与免疫球蛋白以及HLA - A、- B和 - C抗原的相似性。
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