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Dr Billy Hudson et al's article published in Immunology

April 6th 2017

"The susceptible HLA class II alleles and their presenting epitope(s) in Goodpasture's disease".

Xie LJ1,2,3, Cui Z1,2, Chen FJ4, Pei ZY5, Hu SY1,2, Gu QH1,2, Jia XY1,2, Zhu L1,2, Zhou XJ1,2, Zhang H1,2, Liao YH3, Lai LH4, Hudson BG6, Zhao MH1,2,7.

 

Abstract

Goodpasture's disease is closely associated with HLA, particularly DRB1*1501. Other susceptible or protective HLA alleles are not clearly elucidated. The presentation models of epitopes by susceptible HLA alleles are also unclear. We genotyped 140 Chinese patients and 599 controls for 4 digits HLA II genes, and extracted the encoding sequences from IMGT/HLA database. T cell epitopes of α3(IV)NC1 were predicted and the structures of DR molecule-peptide-TCR were constructed. We confirmed DRB1*1501 (OR=4.6, P=5.7×10-28 ) to be a risk allele for Goodpasture's disease. Arginine at position 13 (ARG13) (OR=4.0, P=1.0×10-17 ) and proline at position 11 (PRO11) (OR=4.0, P=2.0×10-17 ) on DRβ1, encoded by DRB1*1501, were associated with disease susceptibility. α134-148 (HGWISLWKGFSFIMF) was predicted as T cell epitope presented by DRB1*1501. Isoleucine137 , tryptophan140 , glycine142 , phenylalanine143 , phenylalanine145 , were presented in peptide-binding pocket 1, 4, 6, 7, 9 of DR2b respectively. ARG13 in pocket 4 interacts with tryptophan140 and forms hydrogen bond. In conclusion, we proposed a mechanism for DRB1*1501 susceptibility for Goodpasture's disease through encoding ARG13 and PRO11 on MHC-DRβ1 chain and presenting T cell epitope, α134-148 , with five critical residues. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

PMID:
28342268
DOI:
10.1111/imm.12736

To read full article, click the link below:

http://onlinelibrary.wiley.com/doi/10.1111/imm.12736/epdf