The susceptible HLA class II alleles and their presenting epitope(s) in Goodpasture's disease.
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 four-digit HLA II genes, and extracted the encoding sequences from the IMGT/HLA database. T-cell epitopes of α3(IV)NC1 were predicted and the structures of DR molecule-peptide-T-cell receptor 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 a T-cell epitope presented by DRB1*1501. Isoleucine137, tryptophan140, glycine142, phenylalanine143and phenylalanine145, were presented in peptide-binding pockets 1, 4, 6, 7 and 9 of DR2b, respectively. ARG13 in pocket 4 interacts with tryptophan140and forms a hydrogen bond. In conclusion, we propose 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.
Renal Division, Peking University First Hospital, Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing, China.|Renal Division, Department of Medicine, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China.
Li-Jun
0000-0002-3973-0516
LJ
Xie
Renal Division, Peking University First Hospital, Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing, China.
Zhao
Z
Cui
State Key Laboratory for Structural Chemistry of Unstable and Stable Species, BNLMS, College of Chemistry and Molecular Engineering and Center for Theoretical Biology, Peking University, Beijing, China.
Fang-Jin
FJ
Chen
Beijing Computing Center, Beijing, China.
Zhi-Yong
ZY
Pei
Renal Division, Peking University First Hospital, Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing, China.
Shui-Yi
SY
Hu
Renal Division, Peking University First Hospital, Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing, China.
Qiu-Hua
0000-0002-3389-5950
QH
Gu
Renal Division, Peking University First Hospital, Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing, China.
Xiao-Yu
XY
Jia
Renal Division, Peking University First Hospital, Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing, China.
Li
L
Zhu
Renal Division, Peking University First Hospital, Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing, China.
Xu-Jie
XJ
Zhou
Renal Division, Peking University First Hospital, Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing, China.
Hong
H
Zhang
Renal Division, Department of Medicine, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, China.
Yun-Hua
YH
Liao
State Key Laboratory for Structural Chemistry of Unstable and Stable Species, BNLMS, College of Chemistry and Molecular Engineering and Center for Theoretical Biology, Peking University, Beijing, China.
Lu-Hua
LH
Lai
Department of Biochemistry, Division of Nephrology and Hypertention, Department of Medicine, Center for Matrix Biology, Aspirnaut Program, Department of Pathology, Microbiology, and Immunology, Department of Cell and Developmental Biology, Vanderbilt Ingram Cancer Centger, Vanderbilt Imstitute of Chemical Biology, Vanderbilt University Medical Center, Nashville, TN, USA.
Billy G
BG
Hudson
Renal Division, Peking University First Hospital, Institute of Nephrology, Peking University, Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing, China.|Peking-Tsinghua Center for Life Sciences, Beijing, China.
Ming-Hui
MH
Zhao
D000483:Alleles; D019867:Anti-Glomerular Basement Membrane Disease / Q000276:immunology*; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D002681:China; D024141:Collagen Type IV / Q000235:genetics / Q000378:metabolism*; D003198:Computer Simulation; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D059811:HLA-DRB1 Chains / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D011110:Polymorphism, Genetic; D011485:Protein Binding; D011487:Protein Conformation; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D012306:Risk; D013601:T-Lymphocytes / Q000276:immunology*
D001324:Autoantigens; D024141:Collagen Type IV; D018984:Epitopes, T-Lymphocyte; D059811:HLA-DRB1 Chains; C489631:HLA-DRB1*15:01 antigen; D011948:Receptors, Antigen, T-Cell; C057112:type IV collagen alpha3 chain

HLA
; 
MHC
; Goodpasture's disease; anti- glomerular basement membrane disease; epitope