Characterization of the T-cell epitope that causes anti-GBM glomerulonephritis.
BACKGROUND
We have demonstrated that a single T-cell epitope pCol(28-40) (SQTTANPSCPEGT) alone, which is derived from NC1 domain of alpha3 chain of type IV collagen (Col4alpha3 NC1), can induce severe glomerulonephritis in Wistar Kyoto rats. This study further characterized this T-cell epitope.


METHODS
A series of synthetic peptides derived from pCol (28-40) were tested in vivo and in vitro for their T-cell epitope activity and nephritogenicity. Major histocompatability complex (MHC) class II molecules in Wistar Kyoto rats were cloned, and MHC restriction of pCol(28-40) was determined.


RESULTS
The T-cell epitope pCol(28-40) was restricted by rat MHC class II RT.1Bl. Ten amino acid residues (29 to 38) were mapped to be the minimum core of the T-cell epitope, which was capable of inducing the T-cell response and severe glomerulonephritis. Only three residues were identified as absolutely critical for the T-cell epitope: position 31 (T) was an anchor residue to the class II molecule, and positions 33 (N) and 34 (P) contributed to the specificity of the T-cell epitope. Thus, only substitution at those positions completely abrogated nephritogenicity of the T-cell epitope. Interestingly, pCol (28-40) also bound to human MHC class II human MHC class II molecule HLA-DRB*1501, which has been linked to human anti-glomerular basement membrane (GBM) disease, suggesting that human homologue of pCol(28-40) could be a potential human T-cell epitope.


CONCLUSIONS
Our study demonstrated that only few residues in the nephritogenic T-cell epitope pCol(28-40) were critical. Our finding also revealed that pCol(28-40) is a potential nephritogenic T-cell epitope in Goodpasture's syndrome.
Robertson
Julie
J
Department of Diagnostic Sciences, Dental Branch, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA.
Wu
Jean
J
Arends
Jon
J
Glass
William
W
Southwood
Scott
S
Sette
Alessandro
A
Lou
Ya-Huan
YH
D000595:Amino Acid Sequence; D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D003001:Cloning, Molecular; D024141:Collagen Type IV / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology / Q000378:metabolism; D059811:HLA-DRB1 Chains; D018716:Molecular Mimicry / Q000276:immunology; D051381:Rats; D011921:Rats, Inbred WKY
D001323:Autoantibodies; D001324:Autoantigens; D024141:Collagen Type IV; D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C489631:HLA-DRB1*15:01 antigen; C057112:type IV collagen alpha3 chain