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. 1986 May;83(10):3121–3125. doi: 10.1073/pnas.83.10.3121

A mouse tumor-specific transplantation antigen is a heat shock-related protein.

S J Ullrich, E A Robinson, L W Law, M Willingham, E Appella
PMCID: PMC323464  PMID: 3458168

Abstract

A tumor-specific transplantation antigen has been purified to homogeneity from the cytosol of a methylcholanthrene-induced tumor, Meth A. The purified antigen is highly immunogenic and specific against challenge with Meth A, providing greater than 95% inhibition of tumor growth in immunized syngeneic mice. Immunofluorescence analysis of Meth A showed that the antigen is a highly abundant cytosolic protein but that it is also present at the cell surface and, therefore, accessible to the host's immune system. The antigen consists of two polypeptide isoforms present in equimolar amounts, having similar masses (84 and 86 kDa), pI values (4.95 and 4.90), and amino acid compositions. Both are phosphoproteins, and neither is glycosylated. The NH2-terminal sequences of the two isoforms are identical except that each chain contains a portion of unique sequence. Comparison of the NH2-terminal and CNBr-fragment sequence data to the sequences of the yeast and Drosophila heat shock proteins (Hsp90 and Hsp83, respectively) reveals that 73 of 91 residues compared are identical. In addition, an anti-Meth A tumor antigen serum that defects the isoforms from a variety of tumors also immunoprecipitates proteins of identical mass and pI from both normal and heat-shocked mouse embryo cells.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bensaude O., Morange M. Spontaneous high expression of heat-shock proteins in mouse embryonal carcinoma cells and ectoderm from day 8 mouse embryo. EMBO J. 1983;2(2):173–177. doi: 10.1002/j.1460-2075.1983.tb01401.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Collins P. L., Hightower L. E. Newcastle disease virus stimulates the cellular accumulation of stress (heat shock) mRNAs and proteins. J Virol. 1982 Nov;44(2):703–707. doi: 10.1128/jvi.44.2.703-707.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. DeLeo A. B., Shiku H., Takahashi T., John M., Old L. J. Cell surface antigens of chemically induced sarcomas of the mouse. I. Murine leukemia virus-related antigens and alloantigens on cultured fibroblasts and sarcoma cells: description of a unique antigen on BALB/c Meth A sarcoma. J Exp Med. 1977 Sep 1;146(3):720–734. doi: 10.1084/jem.146.3.720. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. DuBois G. C., Appella E., Law L. W. Isolation of a tumor-associated transplantation antigen (TATA) from an SV40-induced sarcoma. Resemblance to the TATA of chemically induced neoplasms. Int J Cancer. 1984 Oct 15;34(4):561–566. doi: 10.1002/ijc.2910340420. [DOI] [PubMed] [Google Scholar]
  5. DuBois G. C., Law L. W., Appella E. Purification and biochemical properties of tumor-associated transplantation antigens from methylcholanthrene-induced murine sarcomas. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7669–7673. doi: 10.1073/pnas.79.24.7669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Farrelly F. W., Finkelstein D. B. Complete sequence of the heat shock-inducible HSP90 gene of Saccharomyces cerevisiae. J Biol Chem. 1984 May 10;259(9):5745–5751. [PubMed] [Google Scholar]
  7. Garrels J. I. Two dimensional gel electrophoresis and computer analysis of proteins synthesized by clonal cell lines. J Biol Chem. 1979 Aug 25;254(16):7961–7977. [PubMed] [Google Scholar]
  8. Hackett R. W., Lis J. T. Localization of the hsp83 transcript within a 3292 nucleotide sequence from the 63B heat shock locus of D. melanogaster. Nucleic Acids Res. 1983 Oct 25;11(20):7011–7030. doi: 10.1093/nar/11.20.7011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kadhim S. A., Rees R. C., Barrington-Leigh J. The roles of two peritoneal T-lymphocyte populations in the in vivo rejection of methylcolanthrene-induced sarcoma. Cell Immunol. 1985 Jan;90(1):234–241. doi: 10.1016/0008-8749(85)90185-6. [DOI] [PubMed] [Google Scholar]
  10. Kasambalides E. J., Lanks K. W. Effects of low molecular weight nutrients on the pattern of proteins synthesized by non-proliferating murine L cells. Exp Cell Res. 1981 Mar;132(1):31–39. doi: 10.1016/0014-4827(81)90079-3. [DOI] [PubMed] [Google Scholar]
  11. Kelley P. M., Schlesinger M. J. Antibodies to two major chicken heat shock proteins cross-react with similar proteins in widely divergent species. Mol Cell Biol. 1982 Mar;2(3):267–274. doi: 10.1128/mcb.2.3.267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Khandjian E. W., Türler H. Simian virus 40 and polyoma virus induce synthesis of heat shock proteins in permissive cells. Mol Cell Biol. 1983 Jan;3(1):1–8. doi: 10.1128/mcb.3.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Klein J. H-2 mutations: their genetics and effect on immune functions. Adv Immunol. 1978;26:55–146. doi: 10.1016/s0065-2776(08)60229-1. [DOI] [PubMed] [Google Scholar]
  14. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  15. Lai B. T., Chin N. W., Stanek A. E., Keh W., Lanks K. W. Quantitation and intracellular localization of the 85K heat shock protein by using monoclonal and polyclonal antibodies. Mol Cell Biol. 1984 Dec;4(12):2802–2810. doi: 10.1128/mcb.4.12.2802. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lanks K. W., Kasambalides E. J., Chinkers M., Brugge J. S. A major cytoplasmic glucose-regulated protein is associated with the Rous sarcoma virus pp60src protein. J Biol Chem. 1982 Aug 10;257(15):8604–8607. [PubMed] [Google Scholar]
  17. Law L. W. Changes in tumor-specific antigen expression during passage in vitro and in vivo of newly derived methylcholanthrene-induced sarcomas of BALB/C mice. Int J Cancer. 1980 Feb 15;25(2):251–259. doi: 10.1002/ijc.2910250213. [DOI] [PubMed] [Google Scholar]
  18. Law L. W., Rogers M. J., Appella E. Tumor antigens on neoplasms induced by chemical carcinogens and by DNA- and RNA-containing viruses: properties of the solubilized antigens. Adv Cancer Res. 1980;32:201–235. doi: 10.1016/s0065-230x(08)60362-0. [DOI] [PubMed] [Google Scholar]
  19. Lehto V. P., Virtanen I. Immunolocalization of a novel, cytoskeleton-associated polypeptide of Mr 230,000 daltons (p230). J Cell Biol. 1983 Mar;96(3):703–716. doi: 10.1083/jcb.96.3.703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lowe D. G., Moran L. A. Proteins related to the mouse L-cell major heat shock protein are synthesized in the absence of heat shock gene expression. Proc Natl Acad Sci U S A. 1984 Apr;81(8):2317–2321. doi: 10.1073/pnas.81.8.2317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Morange M., Diu A., Bensaude O., Babinet C. Altered expression of heat shock proteins in embryonal carcinoma and mouse early embryonic cells. Mol Cell Biol. 1984 Apr;4(4):730–735. doi: 10.1128/mcb.4.4.730. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. O'Farrell P. H. High resolution two-dimensional electrophoresis of proteins. J Biol Chem. 1975 May 25;250(10):4007–4021. [PMC free article] [PubMed] [Google Scholar]
  23. RAPPAPORT C. Trypsinization of monkey-kidney tissue: an automatic method for the preparation of cell suspensions. Bull World Health Organ. 1956;14(1):147–166. [PMC free article] [PubMed] [Google Scholar]
  24. Rodenhiser D., Jung J. H., Atkinson B. G. Mammalian lymphocytes: stress-induced synthesis of heat-shock proteins in vitro and in vivo. Can J Biochem Cell Biol. 1985 Jul;63(7):711–722. doi: 10.1139/o85-089. [DOI] [PubMed] [Google Scholar]
  25. Rogers M. J., Appella E., Pierotti M. A., Invernizzi G., Parmiani G. Biochemical characterization of alien H-2 antigens expressed on a methylcholanthrene-induced tumor. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1415–1419. doi: 10.1073/pnas.76.3.1415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Rosenstein M., Eberlein T. J., Rosenberg S. A. Adoptive immunotherapy of established syngeneic solid tumors: role of T lymphoid subpopulations. J Immunol. 1984 Apr;132(4):2117–2122. [PubMed] [Google Scholar]
  27. Welch W. J., Garrels J. I., Thomas G. P., Lin J. J., Feramisco J. R. Biochemical characterization of the mammalian stress proteins and identification of two stress proteins as glucose- and Ca2+-ionophore-regulated proteins. J Biol Chem. 1983 Jun 10;258(11):7102–7111. [PubMed] [Google Scholar]
  28. Willingham M. C. Electron microscopic immunocytochemical localization of intracellular antigens in cultured cells: the EGS and ferritin bridge procedures. Histochem J. 1980 Jul;12(4):419–434. doi: 10.1007/BF01011958. [DOI] [PubMed] [Google Scholar]
  29. Zimmerman C. L., Appella E., Pisano J. J. Rapid analysis of amino acid phenylthiohydantoins by high-performance liquid chromatography. Anal Biochem. 1977 Feb;77(2):569–573. doi: 10.1016/0003-2697(77)90276-7. [DOI] [PubMed] [Google Scholar]

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