Synthetic peptides of Goodpasture's antigen in antiglomerular basement membrane nephritis in rats

The HLA-DRB1*15

“…11 DRB1*15:01 Tg mice were immunized with a1(IV)NC1, a3(IV)NC1, or the E A chimera (containing ha3 [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] or the E B chimera (containing ha3 127-141 overlapping the restricted T cell epitope), and lymphocytes were then re-stimulated with either murine a3 9-28 or a3 129-148 . Mice immunized with a1(IV)NC1 or the E A chimera responded to neither peptide ( Figure 4A), whereas mice immunized with the E B chimera or full-length a3(IV)NC1 responded to a3 129-148 but not a3 [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] . Further groups of mice were immunized with a3(IV)NC1, the E A chimera, or the E B chimera and re-stimulated with chimeric and whole proteins.…”

“…12 However, in the Wistar Kyoto (WKY) rat, T cell reactivity occurs in several different areas. [13][14][15] T cell-mediated disease can be induced by a3 [14][15][16][17][18][19][20][21][22][23][24][25][26] and a3 11-25 15-17 and there is evidence of epitope spreading to involve B cell epitopes. 16,18 Our hypothesis was based on studies in humans with anti-GBM GN showing strong MHC II association and suggesting key epitopes.…”

Mucosal Tolerance Induced by an Immunodominant Peptide from Rat α3(IV)NC1 in Established Experimental Autoimmune Glomerulonephritis

“…Animals treated with pCol (24-38) nasally at 300 g showed no significant reduction in the level of segmental necrosis and/or crescent formation. By contrast, those given pCol(24-38) nasally at 1000 g showed a moderate reduction in severity of the glomerular abnormalities, whereas those given pCol (24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38) at 3000 g showed a marked reduction in the number and severity of the glomerular abnormalities, when compared with positive controls. Negative control animals showed normal renal histology.…”

“…Groups of WKY rats with EAG were given pCol (24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38) nasally at total cumulative doses of 300 g (n ϭ 6), 1000 g (n ϭ 6), or 3000 g (n ϭ 6), over 3 consecutive days after the onset of proteinuria (day 18 after immunization). In addition, positive control groups (POS) (n ϭ 5) (immunized with ␣3(IV)NC1 in FCA) and negative control groups (NEG) (n ϭ 5) (injected with FCA alone) were both given control peptide pCol (38-52) nasally at a total cumulative dose of 3000 g, or saline alone.…”

“…24 -27 Recent studies from our group have identified a 15-mer immunodominant peptide, pCol, (24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38) from the N-terminus of rat ␣3(IV)NC1, which contains the major B-and T-cell epitopes in EAG, and which can induce crescentic nephritis. 24 Previous studies by Luo and colleagues 25 showed that a 24-mer synthetic peptide, pCol, from the N-terminus of ␣3(IV)NC1 was capable of inducing glomerulonephritis, although this was mild and inconsistent, whereas Wu and colleagues 26 showed that a 13-mer peptide, pCol, (28-40) containing a T-cell epitope from ␣3(IV)NC1, induced severe crescentic glomerulonephritis. In further characterization of this T-cell epitope, it was shown that only three residues were critical for disease induction.…”