T cell epitope mimicry in antiglomerular basement membrane disease
JOURNAL OF IMMUNOLOGY
Authors: Arends, J; Wu, J; Borillo, J; Troung, L; Zhou, C; Vigneswaran, N; Lou, YH
Abstract
Antiglomerular basement membrane (GBM) disease or Goodpasture's syndrome is among the earliest recognized human autoimmune diseases. Although collagen 4 alpha 3 NC1 (Col4 alpha 3NC1) has been identified as the responsible autoantigen, it remains unknown how autoimmunity to this autoantigen is provoked. We have demonstrated in our rat model that a single nephritogenic T cell epitope PCol(28-40) of Col4 alpha 3NC1 induces glomerulonephritis. We hypothesized that microbial peptides that mimic this T cell epitope could induce the disease. Based on the critical residue motif (xxtTxNPsxx) of PCol(28-40), seven peptides derived from human infection-related microbes were chosen through GenBank search and synthesized. All peptides showed cross-reactivity with pCol(28-40)-specific T cells at various levels. Only four peptides induced transient proteinuria and minor glomerular injury. However, the other three peptides induced severe proteinuria and modest to severe glomerulonephritis in 16-25% of the immunized rats. Unexpectedly, the most nephritogenic peptide, pCB, derived from Clostridium botulinum, also induced modest (25%) to severe (25%) pulmonary hemorrhage, another important feature of anti-GBM disease; this was not correlated with the severity of glomerulonephritis. This finding suggests that subtle variations in T cell epitope specificity may lead to different clinical manifestations of anti-GBM disease. In summary, our study raises the possibility that a single T cell epitope mimicry by microbial Ag may be sufficient to induce the anti-GBM disease.
Change of uterine histotroph proteins during follicular and luteal phase in pigs
ANIMAL REPRODUCTION SCIENCE
Authors: Lee, Sang-Hee; Song, Eun-Ji; Hwangbo, Yong; Lee, Seunghyung; Park, Choon-Keun
Abstract
The aim of this study was to examine protein expression patterns of uterine histotroph (UH) during the follicular phase (FP) and luteal phase (LP) in pigs. Forty-nine common proteins were identified from FP and LP samples; five were significantly down-regulated (> 1.5-fold), while 15 were significantly up-regulated (> 1.5-fold) in LPUH compared with FPUH (P < 0.05). The 20 differentially-expressed proteins are involved in cell proliferation, cell responses, translation, transport, and metabolism and their molecular functions include nucleic acid binding, oxygen activity, enzymatic activity, growth activity, iron binding, and redox binding. Protein expression of vascular endothelial growth factor D (VEGFD), coatomer subunit gamma-2 (G2COP), collagen alpha 4 chain (COL4), cysteine rich protein 2 (CRP2), myoglobin (MYG), and galactoside 3-L-fucosyltransferase 4 (FUT4) was analyzed by Western blotting. These proteins were significantly higher in LPUH compared to FPUH (P < 0.05). These data expand our understanding of changes in the intrauterine environment during the pre-implantation period in pigs. (C) 2016 Elsevier B.V. All rights reserved.