Insertion Signal Sequence Fused to Minimal Peptides Elicits Specific CD8+ T-Cell Responses and Prolongs Survival of Thymoma-bearing Mice

Boris R. Minev, Barbra J. McFarland, Paul J. Spiess, Steven A. Rosenberg, Nicholas P. Restifo

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

Abstract

CDS+ T-lymphocytes (TCDS+) recognize minimal peptides of 8-10 residues which are the products of intracellularly processed proteins and are presented at the cell surface by major histocompatibility complex class I molecules. An important step in this process is the translocation of processed proteins from the cytosol across the endoplasmic reticulum membrane, mediated by transporter associated with antigen-processing proteins or alternatively by endoplasmic reticulum-insertion signal sequences located at the NH2-terminus of the precursor molecules. We report here that the addition of an endoplasmic reticulum-insertion signal sequence at the NH2-terminus of TCDs+ epitopes from chicken ovalbumin (amino acids 257-264) or a naturally occurring tumor antigen expressed by the murine mastocytoma P815 (P1A amino acids 35-43) significantly enhanced the priming of specific TCDS+ in vivo. The signal sequence did not enhance peptide immunogenicity by merely increasing the hydrophobicity of the peptide, since ovalbumin amino acids 257-264 peptide with the signal sequence at its COOH-terminus did not demonstrate enhanced efficacy. The signal sequence did not act as a helper epitope, since TCDs+ responses were not diminished in class II-deficient transgenic mice or in mice depleted of CD4+ T-cells in vivo. Importantly, a single immunization with the fusion peptide significantly prolonged survival of mice challenged with E.G70VA, a thymoma transfected with the complementary DNA of chicken ovalbumin.

Original languageEnglish (US)
Pages (from-to)4155-4161
Number of pages7
JournalCancer Research
Volume54
Issue number15
StatePublished - Aug 1994

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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