Mouse polyclonal and monoclonal antibody to scrapie-associated fibril proteins

Antibody response in mice to scrapie-associated fibril proteins (protease-resistant proteins [PrPs]) was generated to different epitopes depending on the source of antigen. Mice responded differently to PrPs isolated from scrapie-infected animals of homologous (mouse) versus heterologous (hamster) species. An enzyme-linked immunosorbent assay established to monitor this antibody response in mice immunized with PrPs was unable to detect such a response in scrapie-infected mice. A monoclonal antibody (MAb), 263K 3F4, derived from a mouse immunized with hamster 263K PrPs reacted with hamster but not mouse PrPs. MAb 263K 3F4 also recognized normal host protein of 33 to 35 kilodaltons in brain tissue from hamsters and humans but not from bovine, mouse, rat, sheep, or rabbit brains. This is the first demonstration of epitope differences on this host protein in different species. The defining of various epitopes on PrP through the use of MAbs will lead to a better understanding of the relationship of PrPs to their host precursor protein and to the infectious scrapie agent.

[1]  H. Wiśniewski,et al.  Biochemical differences among scrapie-associated fibrils support the biological diversity of scrapie agents. , 1985, The Journal of general virology.

[2]  J. Parisi,et al.  Clinical and pathological features and laboratory confirmation of Creutzfeldt-Jakob disease in a recipient of pituitary-derived human growth hormone. , 1985, The New England journal of medicine.

[3]  M. M. Bradford.  A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. , 1976, Analytical biochemistry.

[4]  R. Kennedy,et al.  Immune response to hepatitis B surface antigen: enhancement by prior injection of antibodies to the idiotype. , 1983, Science.

[5]  S. Prusiner,et al.  Suppression of polyclonal B cell activation in scrapie-infected C3H/HeJ mice. , 1978, Journal of immunology.

[6]  S. Prusiner,et al.  Scrapie and cellular PrP isoforms are encoded by the same chromosomal gene , 1986, Cell.

[7]  S. Prusiner,et al.  Monoclonal antibodies to the cellular and scrapie prion proteins. , 1986, The Journal of infectious diseases.

[8]  H. Wiśniewski,et al.  Infection-specific particle from the unconventional slow virus diseases. , 1984, Science.

[9]  J. Pumphrey,et al.  Growth of primary plasmacytomas in the mineral oil-conditioned peritoneal environment. , 1972, Journal of the National Cancer Institute.

[10]  W. N. Burnette,et al.  The isolation of hybrid cell lines producing monoclonal antibodies against the p15(E) protein of ecotropic murine leukemia viruses. , 1979, Virology.

[11]  E. Nieschlag,et al.  A method for producing specific antisera with small doses of immunogen. , 1971, The Journal of clinical endocrinology and metabolism.

[12]  M. Shinagawa,et al.  Purification of Scrapie Agent from Infected Animal Brains and Raising of Antibodies to the Purified Fraction , 1986, Microbiology and immunology.

[13]  H. Gelderblom,et al.  Characterization of antisera against scrapie-associated fibrils (SAF) from affected hamster and cross-reactivity with SAF from scrapie-affected mice and from patients with Creutzfeldt-Jakob disease. , 1985, The Journal of general virology.

[14]  R. Lebo,et al.  Human prion protein cDNA: molecular cloning, chromosomal mapping, and biological implications. , 1986, Science.

[15]  P. Brown,et al.  Diagnosis of Creutzfeldt-Jakob disease by Western blot identification of marker protein in human brain tissue. , 1986, The New England journal of medicine.

[16]  H. Wiśniewski,et al.  Detection of scrapie-associated fibril (SAF) proteins using anti-SAF antibody in non-purified tissue preparations. , 1986, The Journal of general virology.

[17]  L. Manuelidis,et al.  Specific proteins associated with Creutzfeldt-Jakob disease and scrapie share antigenic and carbohydrate determinants. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[18]  C. Reading.  In vitro immunization for the production of antigen-specific lymphocyte hybridomas. , 1986, Methods in enzymology.

[19]  H. Diringer,et al.  A rapid and efficient method to enrich SAF-protein from scrapie brains of hamsters , 1984, Bioscience reports.

[20]  C. Masters,et al.  Amyloid plaque core protein in Alzheimer disease and Down syndrome. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[21]  D. Porter,et al.  Failure to demonstrate a humoral immune response to scrapie infection in mice. , 1973, Journal of immunology.

[22]  H. Wiśniewski,et al.  Scrapie-associated fibrils in Creutzfeldt–Jakob disease , 1983, Nature.

[23]  G. C. Millson,et al.  Immunoglobulin G concentrations in the sera of Herdwick sheep with natural scrapie. , 1979, Journal of comparative pathology.

[24]  C. Locht,et al.  Molecular cloning and complete sequence of prion protein cDNA from mouse brain infected with the scrapie agent. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[25]  S. Prusiner,et al.  Antibodies to a scrapie prion protein , 1984, Nature.

[26]  S. Prusiner,et al.  A protease-resistant protein is a structural component of the Scrapie prion , 1983, Cell.

[27]  G. Multhaup,et al.  The protein component of scrapie‐associated fibrils is a glycosylated low molecular weight protein. , 1985, The EMBO journal.

[28]  Ruedi Aebersold,et al.  A cellular gene encodes scrapie PrP 27-30 protein , 1985, Cell.

[29]  N. Robakis,et al.  Isolation of a cDNA clone encoding the leader peptide of prion protein and expression of the homologous gene in various tissues. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[30]  S. Prusiner,et al.  Separation and properties of cellular and scrapie prion proteins. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[31]  H. Gelderblom,et al.  Scrapie infectivity, fibrils and low molecular weight protein , 1983, Nature.