GOODPASTURES EPITOPE IN DEVELOPMENT OF EXPERIMENTAL AUTOIMMUNE GLOMERULONEPHRITIS IN RATS

The Goodpasture's epitope (GP) has recently been localized to the last 36 AA of the non-collagenous (NC1) domain of the alpha(3) chain of ty pe IV collagen [alpha(3),(IV)]. Since alpha(3)(IV) induces glomerulone phritis (GN) in rats and rabbits, the purpose of the present study was to determine if the GP epitope itself could induce GN. We immunized r ats with synthetic peptides of GP epitope, 36-mer, alone or as protein conjugates. Rats immunized with bovine GBM served as positive control s. Peptide immunized rats developed high titer antibodies to peptides, but only unconjugated 36-mer induced antibody against human and bovin e GBM, but not to rat GBM. Acidic residues and the full length 36-mer were important in production of GBM reactive antibodies. Positive cont rols developed antibody to GBM without reactivity against 36-mer, had IgG and fibrin on the basement membrane, GN and proteinuria. Kidney el uted antibody was reactive with rat, bovine, and human GBM but not 36- mer. GN rat lymphocytes underwent blast transformation to GBM but not peptide, and peptide immunized animals responded only to the respectiv e peptides. None of the animals immunized with GP peptide epitope, des pite the development of anti-peptide antibodies or anti-GBM antibodies , developed any in vivo fixation of antibody to the GBM, abnormal prot einuria, or GN. The present study shows that the GP epitope is suffici ent to induce an immune response to the epitope, but it is not suffici ent to induce GN. This demonstrates that other factors or epitopes are important in the pathogenicity of GBM induced GN in this model. These remain to be delineated.