A Mouse Tumor-specific Transplantation Antigen is a Heat Shock-related Protein

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1986 May 1

PMID 3458168

Citations 63

Authors

S J Ullrich

E A Robinson

L W Law

M Willingham

E Appella

Affiliations

Soon will be listed here.

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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References

Rappaport C . Trypsinization of monkey-kidney tissue: an automatic method for the preparation of cell suspensions. Bull World Health Organ. 1956; 14(1):147-66. PMC: 2538109. View

Lai B, Chin N, Stanek A, Keh W, Lanks K . Quantitation and intracellular localization of the 85K heat shock protein by using monoclonal and polyclonal antibodies. Mol Cell Biol. 1984; 4(12):2802-10. PMC: 369291. DOI: 10.1128/mcb.4.12.2802-2810.1984. View

Laemmli U . Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970; 227(5259):680-5. DOI: 10.1038/227680a0. View

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. View

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; 4(4):730-5. PMC: 368789. DOI: 10.1128/mcb.4.4.730-735.1984. View

Rosenstein M, Eberlein T, Rosenberg S . Adoptive immunotherapy of established syngeneic solid tumors: role of T lymphoid subpopulations. J Immunol. 1984; 132(4):2117-22. View

Khandjian E, Turler H . Simian virus 40 and polyoma virus induce synthesis of heat shock proteins in permissive cells. Mol Cell Biol. 1983; 3(1):1-8. PMC: 368497. DOI: 10.1128/mcb.3.1.1-8.1983. View

Rogers M, Appella E, Pierotti M, 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; 76(3):1415-9. PMC: 383262. DOI: 10.1073/pnas.76.3.1415. View

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):173-7. PMC: 555109. DOI: 10.1002/j.1460-2075.1983.tb01401.x. View

10.

Collins P, Hightower L . Newcastle disease virus stimulates the cellular accumulation of stress (heat shock) mRNAs and proteins. J Virol. 1982; 44(2):703-7. PMC: 256315. DOI: 10.1128/JVI.44.2.703-707.1982. View

11.

Garrels J . Two dimensional gel electrophoresis and computer analysis of proteins synthesized by clonal cell lines. J Biol Chem. 1979; 254(16):7961-77. View

12.

DuBois G, Appella E, Law L . 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; 34(4):561-6. DOI: 10.1002/ijc.2910340420. View

13.

Zimmerman C, Appella E, Pisano J . Rapid analysis of amino acid phenylthiohydantoins by high-performance liquid chromatography. Anal Biochem. 1977; 77(2):569-73. DOI: 10.1016/0003-2697(77)90276-7. View

14.

Law L . 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; 25(2):251-9. DOI: 10.1002/ijc.2910250213. View

15.

Lowe D, Moran L . 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; 81(8):2317-21. PMC: 345050. DOI: 10.1073/pnas.81.8.2317. View

16.

Law L, Rogers M, 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; 32:201-35. DOI: 10.1016/s0065-230x(08)60362-0. View

17.

Farrelly F, Finkelstein D . Complete sequence of the heat shock-inducible HSP90 gene of Saccharomyces cerevisiae. J Biol Chem. 1984; 259(9):5745-51. View

18.

Kasambalides E, Lanks K . Effects of low molecular weight nutrients on the pattern of proteins synthesized by non-proliferating murine L cells. Exp Cell Res. 1981; 132(1):31-9. DOI: 10.1016/0014-4827(81)90079-3. View

19.

Hackett R, Lis J . Localization of the hsp83 transcript within a 3292 nucleotide sequence from the 63B heat shock locus of D. melanogaster. Nucleic Acids Res. 1983; 11(20):7011-30. PMC: 326435. DOI: 10.1093/nar/11.20.7011. View

20.

Willingham M . Electron microscopic immunocytochemical localization of intracellular antigens in cultured cells: the EGS and ferritin bridge procedures. Histochem J. 1980; 12(4):419-34. DOI: 10.1007/BF01011958. View