T cell responses to peptides of Goodpasture autoantigen in patients with anti-glomerular basement membrane disease.
OBJECTIVE
Cell-mediated autoimmunity, especially autoreactive T cells, is crucial in the initiation of anti-glomerular membrane (GBM) disease. Epitopes for T cells on Goodpasture autoantigen are not fully defined. This study investigated T cell epitopes in anti-GBM patients, aiming to identify the epitopes and their clinical significance.


METHODS
Peripheral blood mononuclear cells (PBMC) were collected from 13 patients with anti-GBM disease. Twenty-four overlapping linear peptides were synthesized covering the whole sequence of human α3(IV)NC1. PBMC response to each peptide was detected by proliferation assay. Their associations with clinical features were further analyzed.


RESULTS
Peripheral blood mononuclear cells proliferative responses to linear peptides on α3(IV)NC1 could be detected in all patients. Five major epitopes were identified as stimulatory in over half of the patients: α3(IV)NC1127-148(P14) (69.2%), α3(IV)NC1159-178(77.8%), α3(IV)NC1179-198(55.6%), α3(IV)NC1189-208(P19) (75.0%) and α3(IV)NC1141-154(57.1%). P14 and P19 were highly recognized in patients comparing with healthy controls (69.2% vs. 0.0%, P = 0.011; 75.0% vs. 0.0%, P = 0.021, respectively).


CONCLUSIONS
T cell proliferation to linear epitopes was detected in human anti-GBM disease. α3127-148was a mutual T and B cell epitope, implying its initial role in epitope spreading process.
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.|Department of Nephrology, Tianjin Medical University General Hospital, Tianjin, 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.
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.
Qiu-Hua
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.
Chong-Yan
CY
Yu
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-Yang
XY
Cheng
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.
Qi-Zhuang
QZ
Jin
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.
Fu-De
FD
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.
Zhao
Z
Cui
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
D000328:Adult; D019867:Anti-Glomerular Basement Membrane Disease / Q000097:blood / Q000276:immunology*; D001324:Autoantigens / Q000097:blood / Q000276:immunology*; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016022:Case-Control Studies; D049109:Cell Proliferation; D002478:Cells, Cultured; D024141:Collagen Type IV / Q000097:blood / Q000276:immunology*; D018604:Epitope Mapping; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D016056:Immunodominant Epitopes; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
D001324:Autoantigens; D024141:Collagen Type IV; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; C057112:type IV collagen alpha3 chain
Goodpasture antigen; T cell; anti-GBM disease; epitope; kidney injury