Membranes activate tumor- and virus-specific precursor cytotoxic T lymphocytes in vivo and stimulate tumor-specific T lymphocytes in vitro: implications for vaccination

J Immunother Emphasis Tumor Immunol. 1994 Apr;15(3):165-74. doi: 10.1097/00002371-199404000-00002.

Abstract

Plasma membranes contain the entire antigenic repertoire of a cell in the form of processed antigens presented as peptides by major histocompatibility complex (MHC) class I molecules. We report here that plasma membranes but not internal membranes of cognate tumors stimulate murine fibrosarcoma and human melanoma-specific cytotoxic T lymphocyte (CTL) clones in vitro in an antigen-specific. MHC class I-restricted manner. Although stimulation of CTLs by class I-peptide complexes on reconstituted membranes has been documented before, this is the first demonstration of stimulation of cloned CTLs by natural, endogenously processed MHC class I-peptide complexes on plasma membranes. In addition to their ability to stimulate CTLs in vitro, immunization of syngeneic mice with membranes derived from ultraviolet-induced tumor cells, SV40 transformed fibroblasts, or influenza-infected fibroblasts elicits an antigen-specific, MHC class I restricted primary CTL response. To the best of our knowledge, this is also the first demonstration of the ability of cellular membranes to prime an MHC class I-restricted CTL responses in vivo. The ability of membranes to prime a CTL response in vivo suggests that they may be used as T-cell vaccines against tumors or infectious viruses. This approach circumvents the difficulties in generation of human tumor cell lines and identification of CTL-recognized determinants for vaccination and avoids some of the risks associated with whole-cell vaccination such as inoculation of patients with immunosuppressive factors, transforming DNA, or infectious viruses.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Cell Membrane / immunology*
  • Hematopoietic Stem Cells / immunology*
  • Histocompatibility Antigens Class I / physiology
  • Lymphocyte Activation*
  • Mice
  • Mice, Inbred C3H
  • Neoplasms / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Vaccination*
  • Viruses / immunology

Substances

  • Histocompatibility Antigens Class I