z-logo
open-access-imgOpen Access
The pathogenicity of T cell epitopes on human Goodpasture antigen and its critical amino acid motif
Author(s) -
Hu Shuiyi,
Gu Qiuhua,
Wang Jia,
Wang Miao,
Jia Xiaoyu,
Cui Zhao,
Zhao Minghui
Publication year - 2017
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13134
Subject(s) - epitope , antigen , antibody , glomerulonephritis , microbiology and biotechnology , biology , chemistry , immunology , endocrinology , kidney
Goodpasture antigen, the non‐collagenous domain of α3 chain of type IV collagen [α3(IV)NC1], is the target antigen of anti‐glomerular basement membrane (GBM) antibodies. The pathogenicity of T cell epitopes is not elucidated clearly. In this study, we aim to define the nephritogenic T cell epitopes and its critical amino acid residues. Twenty‐four overlapping linear peptides were synthesized covering the whole sequence of human α3(IV)NC1. Wistar–Kyoto rats were immunized with linear peptides, and experimental autoimmune glomerulonephritis was evaluated. Critical amino acid was identified by the loss of nephritogenic function after each amino acid substitution by alanine. Of the 24 peptides, P14 (α3 127‐148 ) could induce 90.5% (19/21) of WKY rats developing anti‐GBM glomerulonephritis with proteinuria, elevated serum urea and creatinine, IgG linear deposit on GBM and substantial (in average 82.4 ± 5.6%) crescent formation in glomeruli. Lymphocytes of immunized rats proliferated in response to α3 127‐148 and α3(IV)NC1 in vitro . Sera of these rats recognized α3 127‐148 and later on together with intact human α3(IV)NC1. Antibodies towards α3 127‐148 and intact α3(IV)NC1 could also be detected from the kidney elutes. These antibodies showed no cross‐reaction with each other, which implies intramolecular epitope spreading during disease progress. After sequential amino acid substitution, the α3 127‐148 with substitution of tryptophan 136 , isoleucine 137 , leucine 139 or tryptophan 140 lost its nephritogenicity. Human α3 127‐148 is a nephritogenic T cell epitope in WKY rats, with the critical amino acids as W 136 I 137 xL 139 W 140 . These findings might facilitate future investigation on microbial aetiology and potential specific immunotherapy of anti‐GBM disease.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.
Having issues? You can contact us here