Induction and persistence of a cytotoxic T lymphocyte (CTL) response against a herpes simplex virus-specific CTL epitope expressed in a cellular protein

Tong Ming Fu, Robert H. Bonneau, Melanie Epler, M. Judith Tevethia, Samina Alam, Keith Verner, Satvir S. Tevethia

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Abstract

CD8+ cytotoxic T-lymphocytes recognize small epitope peptides in association with MHC class I molecules expressed on the cell surface. In this study, we have determined whether an 8 amino acid viral CTL epitope, when expressed in a cellular protein, can be appropriately processed, presented, and recognized by the corresponding epitope-specific CTL and whether it is capable of inducing a CTL response in vivo. An H-2Kb-restricted CTL epitope from herpes simplex virus type 1 (HSV-1) glycoprotein B (gB epitope, residues 498-505) was cloned into the mouse dihydrofolate reductase protein (DHFR) at amino acid position 87. The recombinant DHFRs were expressed in vaccinia virus recombinants. To distinguish the recombinant DHFR proteins from the endogenous DHFR, an antibody epitope, recognized by monoclonal antibody PAb 901 and derived from simian virus 40 (SV40) T antigen was tagged to the C-termini of recombinant DHFR proteins. In vivo expression of recombinant DHFR was demonstrated by immunoprecipitation with the monoclonal antibody PAb 901. The H-2b cells infected with recombinant vaccinia virus expressing the recombinant DHFR were specifically lysed by gB epitope-specific CTL. Furthermore, the recombinant DHFR was functional in inducing a long lasting HSV gB epitope-specific CTL response upon immunization of C57BL/6 (B6) mice. These results indicate that a viral epitope expressed in a cellular protein can be efficiently processed, presented, and recognized by epitope-specific CTL and show that cellular proteins expressing CTL epitopes can be used for induction of CD8+ T lymphocyte responses.

Original languageEnglish (US)
Pages (from-to)269-274
Number of pages6
JournalVirology
Volume222
Issue number1
DOIs
StatePublished - Aug 1 1996

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T-Lymphocyte Epitopes
Cytotoxic T-Lymphocytes
Simplexvirus
Tetrahydrofolate Dehydrogenase
Epitopes
Proteins
Vaccinia virus
Monoclonal Antibodies
Amino Acids
Simian virus 40
Viral Tumor Antigens
Human Herpesvirus 1
Immunoprecipitation
Immunization

All Science Journal Classification (ASJC) codes

  • Virology

Cite this

Fu, Tong Ming ; Bonneau, Robert H. ; Epler, Melanie ; Tevethia, M. Judith ; Alam, Samina ; Verner, Keith ; Tevethia, Satvir S. / Induction and persistence of a cytotoxic T lymphocyte (CTL) response against a herpes simplex virus-specific CTL epitope expressed in a cellular protein. In: Virology. 1996 ; Vol. 222, No. 1. pp. 269-274.
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Induction and persistence of a cytotoxic T lymphocyte (CTL) response against a herpes simplex virus-specific CTL epitope expressed in a cellular protein. / Fu, Tong Ming; Bonneau, Robert H.; Epler, Melanie; Tevethia, M. Judith; Alam, Samina; Verner, Keith; Tevethia, Satvir S.

In: Virology, Vol. 222, No. 1, 01.08.1996, p. 269-274.

Research output: Contribution to journalArticle

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