Functional analysis of amino acid residues encompassing and surrounding two neighboring H-2Db-restricted cytotoxic T-lymphocyte epitopes in simian virus 40 tumor antigen.

We transiently expressed adenovirus type C E1a proteins in wild-type or mutant form from plasmid vectors which have different combinations of E1a and simian virus 40 enhancer elements and which contain the DNA replication origin of SV40 and can replicate in COS 7 cells. We measured the levels of E1a mRNA encoded by the vectors and the transition regulation properties of the protein products. Three vectors encoded equivalent levels of E1a mRNA in COS 7 cells: (i) a plasmid encoding the wt 289-amino acid E1a protein (this complemented the E1a deletion mutant dl312 for early region E2a expression under both replicative and nonreplicative conditions); (ii) a vector for the wt 243-amino acid E1a protein (this complemented dl312 weakly and only under conditions of high multiplicities of dl312); (iii) a mutant, pSVXL105, in which amino acid residues-38 through 44 of the 289-amino acid E1a protein (which includes two highly conserved residues) are replaced by 3 novel amino acids (this also complemented dl312 efficiently). A fourth vector, mutant pSVXL3 with which linker substitution shifts the reading frame to encode a truncated 70-amino acid fragment from the amino terminus of the 289-amino acid protein, was unable to complement dl312. Surprisingly, pSVXL3 overexpressed E1a mRNA approximately 30-fold in COS 7 cells in comparison with the other vectors. The pSVXL3 overexpression could be reversed by cotransfection with a wt E1a vector. We suggest that wt E1a proteins regulate the levels of their own mRNAs through the recently described transcription repression functions of the 289- and 243-amino acid E1a protein products and that pSVXL3 fails to autoregulate negatively.

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Frequency Analysis of Simian Virus 40-specific Cytotoxic T Lymphocyte Precursors in the High Responder C57BL/6 Mouse Strain

Journal of General Virology ◽

10.1099/0022-1317-69-10-2493 ◽

1988 ◽

Vol 69 (10) ◽

pp. 2493-2503 ◽

Cited By ~ 8

Author(s):

S. R. Jennings ◽

K. L. Fresa ◽

P. A. Lippe ◽

J. E. Milici ◽

S. S. Tevethia

Keyword(s):

T Lymphocyte ◽

Frequency Analysis ◽

Mouse Strain ◽

Cytotoxic T Lymphocyte ◽

Simian Virus 40 ◽

Simian Virus ◽

High Responder

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Simian virus 40 T antigen as a carrier for the expression of cytotoxic T-lymphocyte recognition epitopes.

Journal of Virology ◽

10.1128/jvi.67.11.6866-6871.1993 ◽

1993 ◽

Vol 67 (11) ◽

pp. 6866-6871 ◽

Cited By ~ 5

Author(s):

T M Fu ◽

R H Bonneau ◽

M J Tevethia ◽

S S Tevethia

Keyword(s):

T Lymphocyte ◽

Cytotoxic T Lymphocyte ◽

Simian Virus 40 ◽

Simian Virus ◽

T Antigen

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Dissection of H-2Db-restricted cytotoxic T-lymphocyte epitopes on simian virus 40 T antigen by the use of synthetic peptides and H-2Dbm mutants.

Journal of Virology ◽

10.1128/jvi.64.3.1192-1200.1990 ◽

1990 ◽

Vol 64 (3) ◽

pp. 1192-1200 ◽

Cited By ~ 20

Author(s):

S S Tevethia ◽

M Lewis ◽

Y Tanaka ◽

J Milici ◽

B Knowles ◽

...

Keyword(s):

T Lymphocyte ◽

Synthetic Peptides ◽

Cytotoxic T Lymphocyte ◽

Simian Virus 40 ◽

Simian Virus ◽

T Antigen

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Cytotoxic T-Lymphocyte Epitope Immunodominance in the Control of Choroid Plexus Tumors in Simian Virus 40 Large T Antigen Transgenic Mice

Journal of Virology ◽

10.1128/jvi.73.7.5981-5993.1999 ◽

1999 ◽

Vol 73 (7) ◽

pp. 5981-5993 ◽

Cited By ~ 40

Author(s):

Todd D. Schell ◽

Lawrence M. Mylin ◽

Ingo Georgoff ◽

Angelica K. Teresky ◽

Arnold J. Levine ◽

...

Keyword(s):

Transgenic Mice ◽

Choroid Plexus ◽

T Lymphocyte ◽

Adoptive Transfer ◽

Cytotoxic T Lymphocyte ◽

Simian Virus 40 ◽

Simian Virus ◽

Spleen Cells ◽

Spontaneous Tumors ◽

Specific Ctls

ABSTRACT The simian virus 40 (SV40) large tumor antigen (Tag) is a virus-encoded oncoprotein which is the target of a strong cytotoxic T-lymphocyte (CTL) response. Three immunodominant H-2b-restricted epitopes, designated epitopes I, II/III, and IV, have been defined. We investigated whether induction of CTLs directed against these Tag epitopes might control Tag-induced tumors in SV11+ (H-2b ) mice. SV11+ mice develop spontaneous tumors of the choroid plexus due to expression of SV40 Tag as a transgene. We demonstrate that SV11+ mice are functionally tolerant to the immunodominant Tag CTL epitopes. CTLs specific for the H-2Kb-restricted Tag epitope IV were induced in SV11+ mice following adoptive transfer with unprimed C57BL/6 spleen cells and immunization with recombinant vaccinia viruses expressing either full-length Tag or the H-2Kb-restricted epitope IV as a minigene. In addition, irradiation of SV11+ mice prior to adoptive transfer with unprimed C57BL/6 spleen cells led to the priming of epitope IV-specific CTLs by the endogenous Tag. Induction of epitope IV-specific CTLs in SV11+ mice by either approach correlated with increased life span and control of the choroid plexus tumor progression, indicating that CTLs specific for the immunodominant Tag epitope IV control the progressive growth of spontaneous tumors induced by this DNA virus oncogene in transgenic mice.

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