Nephritogenicity and alpha-chain composition of NC1 fractions of type IV collagen from bovine renal basement membrane

Nephritogenicity (anti-GBM-nephritis-inducing activity) and alpha-chain composition of globular-domain (NC1) fractions of type IV collagen from bovine renal, pulmonary, and placental basement membranes (BMs) was examined by injecting these fractions with adjuvant into WKY/NCrj rats and by Western blotting using epitope-defined monoclonal antibodies to the six different a chains of type IV collagen. A purified nephritogenic fraction from renal BM contained alpha 1-alpha 6(IV)NC1, whereas a non-nephritogenic fraction contained only alpha 1-alpha 2(IV)NC1. Renal and pulmonary NC1 had strong nephritogenic activity; placental NC1 had weak activity. The renal and pulmonary fractions contained alpha 1-alpha 6(IV)NC1, and the placental fraction had a large amount of alpha 1-alpha 2(IV)NC1 and a very small amount of alpha 3-alpha 6(IV)NC1. Immunohistochemical study of bovine renal EM with the monoclonal antibodies revealed that bovine glomerular BM contained alpha 1-alpha 5(IV) chains, but not the alpha 6(IV) chain. The absence of alpha 6(IV) chain in glomerular BM in bovine and in humans indicates that alpha 6(IV) chain is not a target antigen of anti-GBM nephritis. Nephritogenicity is apparently a property of alpha 3-alpha 5(IV)NC1.