Isolation and characterization of the nephritogenic antigen producing anti-tubular basement membrane disease.

Abstract

The use of purified self-antigens can facilitate the further analysis of pathogenic mechanisms in autoimmunity (1, 2). This report describes the isolation of the nephritogenic antigen of anti-tubular basement membrane (a-TBM)l-induced interstitial nephritis.

Specific Changes in the Basement Membrane of the Proximal Tubules in the Murine Polycystic Kidney Detected by the Novel Anti-basement Membrane Monoclonal Antibody D28

“…Among these mAbs and polyclonal antibodies, the LAM-2 [21] and Lam-2 [20] mAbs, the 3M-lglycoprotein polyclonal antibody [5,241, and our novel D28 mAb have a similar specificity in that they do not react with the BM of the distal tubules. Unlike the other antibodies, however, the D28 mAb does not react with the BM of the Bowman's capsule [5,20,21,24] . It is therefore highly specific to BM of the proximal tubules.…”

Inhibition of murine nephritogenic effector T cells by a clone-specific suppressor factor.

“…Soluble renal tubular antigen (SRTA) was made from these lyophilized membranes by collagenase digestion (28). The nephritogenic moiety in this digestion, the 3M-I glycoprotein, is purified from SRTA using immunoaffinity chromatography with a mAb (25). P1, a synthetic peptide derived from the cDNA sequence of 3M-1 (LLRRRHGDRRSTMSAEVP) was manually synthesized by the simultaneous multiple peptide method of Houghten (29,30 T cell lines (M52 and M61) and clones.…”

“…We have recently characterized a panel of nephritogenic effector T cell clones specific for 3M-1, a glycoprotein target antigen of aTBM disease (25,26). These cultured CD8+ T cells, called M52, maintain the functional capacity of nephritogenic effector T cells induced in vivo (26).…”

Tubular antigen-binding proteins repress transcription of type IV collagen in the autoimmune target epithelium of experimental interstitial nephritis.

“…MCT cells in culture secrete measurable amounts of basement membrane type IV collagen, as well as lesser amounts of interstitial types I and III collagens (7). Since much of the cortical tubular architecture of the kidney undergoes destructive remodelling during autoimmune interstitial inflammation (13,14), and since our ThF recognizes an autoantigen distributed only along cortical tubules (3,4), we attempted in this report to determine what biologic effect ThF might have on the transcription and secretion oftypes I and IV collagens by MCT epithelium in culture.…”

“…These early experiments suggested the possibility of interactions between immune and somatic cells. Since that time we have been able to both characterize the relevant nephritogenic 3M-1 target antigen (3,4) as well as establish 3M-1-specific CD4' helper T cell clones (5). These helper T cells are present within inflammatory tubulointerstitial infiltrates (5), secrete a 3M-1-binding protein (ThF)' of -78,000 Mr (6), and recognize 3M-I on the surface of cultured proximal tubular epithelium (MCT cells;7,8) from the kidney.…”