The critical amino acids of a nephritogenic epitope on human Goodpasture   autoantigen for binding to HLA-DR131*1501

doi:10.1016/j.molimm.2017.05.011

CORC > 北京大学 > 化学与分子工程学院

	*The critical amino acids of a nephritogenic epitope on human Goodpasture autoantigen for binding to HLA-DR1311501**
	Gu, Qiu-hua ; Jia, Xiao-yu ; Li, Jian-nan ; Chen, Fang-jin ; Cui, Zhao ; Zhao, Ming-hui
刊名	MOLECULAR IMMUNOLOGY
	2017
关键词	Anti-GBM disease HLA-DRB1*1501 Peptide Binding capacity BASEMENT-MEMBRANE ANTIBODY T-CELL EPITOPE ALPHA-3(IV) COLLAGEN PEPTIDE BINDING GBM NEPHRITIS NC1 DOMAIN DISEASE GLOMERULONEPHRITIS IDENTIFICATION CHAIN
DOI	10.1016/j.molimm.2017.05.011
英文摘要	Background: Anti-GBM disease is caused by autoimmunity to Goodpasture antigen on alpha 3(IV)NC1 and had strong associations with HLA-DRB11501. Previous studies identified alpha 3(127-148) (P14: TDIPPCPHGWISLWKGFSFIMF) as a T cell epitope. The present study was aimed to investigate the binding capacity of P14 to HLA-DRB11501 and the critical amino acids for this binding. Methods: A line of EBV-transformed human B cells homozygous for HLA-DRB11501 was used to detect the binding capacity of peptides to HLA-DRB11501 using flow cytometry analysis. P14 was sequentially truncated into 8 peptides with 15 amino acids to identify the core binding motif. A set of alanine substituted peptides of P14-2 was then synthesized to identify its critical residues for binding to HLA-DRB11501. The structure of HLA-DR2b-Peptide-TCR complex was constructed by modeling to analyze the interaction of each amino acids of P14-2 with the HLA-DR2b molecule. Results: P14 could bind to HLA-DRB11501 expressed on B cell surface. The N-terminus of P14 was the core binding motif and the truncated peptide P14-2 (DIPPCPHGWISLWKG) (128-142) had the strongest binding capacity. After sequential amino acid substitution, we found the binding capacity of P14-2 was completely lost by the substitution of cysteine (C) (132) and significantly decreased by the substitution of tryptophan (W) 136, lysine (K) (141), or glycine (G) (142), but still at a high level. The modeling showed that (C) (132) had a strong interaction with pocket 4 on the beta chain of DR2b. Thus, C-132, W (136), K-141, and G(142) were defined as the critical amino acid residues for the binding capacity of P14 to HLA-DRB11501. Conclusion: We identified alpha 13(128-142) (DIPPCPHGWISLWKG) as the core binding motif of P14 to HLA-DRB11501 molecule. And the critical amino acid residues for this binding were further defined as C-132, W (136), K (141), and G (142).; Natural Science Foundation of China [81621092, 81622009, 81330020, 81370801, 81400703]; SCI(E); ARTICLE; 1-9; 88
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/471747]
专题	化学与分子工程学院
推荐引用方式 GB/T 7714	Gu, Qiu-hua,Jia, Xiao-yu,Li, Jian-nan,et al. The critical amino acids of a nephritogenic epitope on human Goodpasture autoantigen for binding to HLA-DR131*1501[J]. MOLECULAR IMMUNOLOGY,2017.
APA	Gu, Qiu-hua,Jia, Xiao-yu,Li, Jian-nan,Chen, Fang-jin,Cui, Zhao,&Zhao, Ming-hui.(2017).The critical amino acids of a nephritogenic epitope on human Goodpasture autoantigen for binding to HLA-DR131*1501.MOLECULAR IMMUNOLOGY.
MLA	Gu, Qiu-hua,et al."The critical amino acids of a nephritogenic epitope on human Goodpasture autoantigen for binding to HLA-DR131*1501".MOLECULAR IMMUNOLOGY (2017).