Mapping of the genes for tubular basement membrane antigen and a submaxillary gland protease in the rat

Matsumoto, Kozo; McCafferty, E; Gasser, David L.

doi:10.1007/bf00364483

Cited by 21 publications

(4 citation statements)

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“…LEW rats lack this determinant (and are consequently protected from the induction of a-TBM disease), and genetic mapping suggests that the relevant locus exists on a non-MHC chromosome (12). Very recent data (13) indicate that the gene for the TBM nephrito-genic antigen exists in the first linkage group of the rat, which is homologous to chromosome 7 of the mouse.…”

Section: Discussionmentioning

confidence: 99%

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

Clayman

Martínez-Hernández²,

Michaud

et al. 1985

The Journal of Experimental Medicine

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Section: Discussionmentioning

confidence: 99%

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

Clayman

Martínez-Hernández²,

Michaud

et al. 1985

The Journal of Experimental Medicine

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“…Eventually some isoforms of 3M-1 are translocated to the lateral border of the proximal tubular basement membrane in vivo (4). The genes for 3M-1 map to the first (6) and fourth (7) linkage groups in rats and probably to chromosome VII in mice (6). The 3M-1 protein has been purified immunochemically from rabbits (4), mice (5), rats (8), and humans (9).…”

mentioning

confidence: 99%

Molecular characterization of a major nephritogenic domain in the autoantigen of anti-tubular basement membrane disease.

Neilson

Sun

Kelly

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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Anti-tubular basement membrane (aTBM) disease is a form of primary interstitial nephritis mediated by autoimmune T cells and aTBM antibodies. In mice and humans the nephritogenic immune response is directed to a glycoprotein (3M-1) found along the proximal tubule of the kidney. We have isolated cDNAs from an expression library that encodes for the common framework domain of the 3M-1 antigen. This common domain was once related evolutionarily to a family of intermediate filament-associated proteins. Northern hybridization revealed that all isoforms of 3M-1 range between 1700 and 1900 base pairs and in situ hybridization studies indicate that transcripts are found in tubular epithelium. Candidate peptide fragments were deduced and synthesized from the sequence encoding this common framework domain, and one of the peptide residues was able to bind a monoclonal 3M-1-reactive aTBM antibody, stimulate the growth of 3M-1-reactive helper T cells, and induce nephritogenic effector T cells capable of producing interstitial nephritis.Our results indicate that a unique, immunodominant region of the 3M-1 antigen is an informative participant in the emergence of autoimmune inJury to certain basement membranes.Inflammatory interstitial nephritis, either as a primary or secondary process, plays a central role in the progressive development of nearly all forms of chronic renal failure (1). Very little, however, is known about the target antigens that focus injury toward parenchymal structures residing in the tubulointerstitium. Our laboratory has been studying this problem using a rodent model of human interstitial nephritis called anti-tubular basement membrane (aTBM) disease. aTBM disease develops in mice or rats following their immunization with renal tubular basement membranes in adjuvant (2,3). aTBM antibodies (aTBM-Abs/a3M-1-Abs) develop over 7-10 days, and extensive mononuclear infiltrates with tubular atrophy and fibrosis appear within several weeks.The target antigen of this disease, the 3M-1 glycoprotein (4), is expressed in mice on nearly all cortical tubular basement membranes and by cultured proximal tubular epithelium (MCT cells). It can be found intracellularly, on their cell surface, or in the culture supernatant as a secreted product of -30,000 Mr (5). Eventually some isoforms of 3M-1 are translocated to the lateral border of the proximal tubular basement membrane in vivo (4). The genes for 3M-1 map to the first (6) and fourth (7) linkage groups in rats and probably to chromosome VII in mice (6). The 3M-1 protein has been purified immunochemically from rabbits (4), mice (5), rats (8), and humans (9).The nephritogenic autoimmune response has also been characterized in mice, rats, and humans with polyclonal antisera (2, 8-11), by constructing monoclonal aTBM-Abs reactive to 3M-1 (Ma3M-1-Abs; refs 4, 10), and by establishing tubular antigen (3M-1)-specific CD4' helper (12,13) and CD8' effector T clones (14) that recognize 3M-1 on the surface of MCT cells (5, 15) or as a soluble moiety processed by tradition...

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“…In this model, prototypically susceptible Brown Norway (BN) rats immunized with rabbit, but not with BN, renal tubular antigens develop anti-tubular basement membrane antibodies (a-TBM-Ab) and an intense mononuclear cell infiltrate producing severe interstitial nephritis. Previously, we showed that susceptibility to this lesion in rats principally requires both the genetically determined expression of the relevant cortical tubular antigen (TBM +) (7,8) and the capacity to mount an MHC-linked, cell-mediated immune response to the antigen (7). We now demonstrate that the induction of tolerance to TBM first requires antigen This work was supported by a Basil O'Connor Grant from The March of Dimes-Birth Defects Foundation and, in part, by grants AM-07006, AM-30280, AM-20553, and CA-18640 from the National Institutes of Health.…”

Section: From the Renal-electrolyte Section Of The Department Of Medicine And The Department Of Human Genetics University Of Pennsylvaniamentioning

confidence: 99%

Tolerance to parenchymal self. Regulatory role of major histocompatibility complex-restricted, OX8+ suppressor T cells specific for autologous renal tubular antigen in experimental interstitial nephritis.

Kelly¹,

Silvers²

1985

The Journal of Experimental Medicine

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New information continues to emerge regarding basic immunologic mechanisms of self-tolerance. While tolerance is often defined at the T or B cell level (1), the overall process can also be categorized by mechanisms mediated either by the deletion of self-reactive clones, the effects of suppressor T cell surveillance, or the sequential action of both processes (2). Such mechanisms have been intensively analyzed in the context of strategies designed to induce immunologic unresponsiveness to histocompatibility antigens on lymphocytes, skin, and most transplantable organs (3-6). Current evidence, however, has not directly established whether such findings can be extended to the prevention of antigenspecific autoimmunity to non-major histocompatibility complex (MHC) 1 parenchymal self.Therefore, taking advantage of the genetic polymorphisms that are involved with the susceptibility of rats to autoimmune interstitial nephritis (7), we have investigated the mechanism of tolerance to autologous renal tubular antigen. In this model, prototypically susceptible Brown Norway (BN) rats immunized with rabbit, but not with BN, renal tubular antigens develop anti-tubular basement membrane antibodies (a-TBM-Ab) and an intense mononuclear cell infiltrate producing severe interstitial nephritis. Previously, we showed that susceptibility to this lesion in rats principally requires both the genetically determined expression of the relevant cortical tubular antigen (TBM +) (7,8) and the capacity to mount an MHC-linked, cell-mediated immune response to the antigen (7). We now demonstrate that the induction of tolerance to TBM first requires antigen

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Mapping of the genes for tubular basement membrane antigen and a submaxillary gland protease in the rat

Cited by 21 publications

References 11 publications

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

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

Molecular characterization of a major nephritogenic domain in the autoantigen of anti-tubular basement membrane disease.

Tolerance to parenchymal self. Regulatory role of major histocompatibility complex-restricted, OX8+ suppressor T cells specific for autologous renal tubular antigen in experimental interstitial nephritis.

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