IDENTIFICATION OF A CDNA-ENCODING TUBULOINTERSTITIAL NEPHRITIS ANTIGEN

Tubulointerstitial nephritis antigen (TIN-ag) is a 58-kDa basement mem brane glycoprotein that is recognized by human autoantibodies in certa in forms of tubulointerstitial nephritis. To further characterize this macromolecule and isolate cDNAs encoding TIN-ag, amino acid sequences from tryptic peptides were used to design and synthesize primers in o rder to amplify a probe for screening a rabbit kidney cortex cDNA libr ary, A cDNA encoding TIN-ag was cloned and sequenced. The predicted am ino acid sequence deduced from this cDNA includes the chemically deter mined sequences of peptides derived from TIN-ag, supporting its authen ticity. The predicted amino acid sequence also shows that the carboxyl -terminal region of the molecule exhibits a 30% homology with human pr eprocathepsin B, a member of the cysteine proteinase family of protein s, A domain in the amino-terminal region of TIN-ag contains an epiderm al growth factor-like motif that shares homology with laminin A and S chains, alpha 1 chain of type I collagen, von Willebrand's factor, and mucin, suggesting structural and perhaps functional similarities amon g these molecules, Immunoprecipitation of in vitro generated recombina nt protein using a TIN-ag-specific monoclonal antibody (AS), confirms the identity of the isolated TIN-ag cDNA, In this report the cDNA and predicted amino acid sequences of TIN-ag are presented, Knowledge of t he primary structure of TIN-ag will facilitate our understanding of th e molecular structure of this novel basement membrane component and ma y provide clues toward understanding its functional role.