Antigen-loaded ER microsomes from APC induce potent immune responses against viral infection

Eur J Immunol. 2009 Jan;39(1):85-95. doi: 10.1002/eji.200838443.

Abstract

Although matured DC are capable of inducing effective primary and secondary immune responses in vivo, it is difficult to control the maturation and antigen loading in vitro. In this study, we show that ER-enriched microsomal membranes (microsomes) isolated from DC contain more peptide-receptive MHC I and II molecules than, and a similar level of costimulatory molecules to, their parental DC. After loading with defined antigenic peptides, the microsomes deliver antigenic peptide-MHC complexes (pMHC) to both CD4 and CD8 T cells effectively in vivo. The peptide-loaded microsomes accumulate in peripheral lymphoid organs and induce stronger immune responses than peptide-pulsed DC. The microsomal vaccines protect against acute viral infection. Our data demonstrate that peptide-MHC complexes armed microsomes from DC can be an important alternative to DC-based vaccines for protection from viral infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation*
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / virology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / virology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / virology
  • Dendritic Cells / immunology
  • Endoplasmic Reticulum / immunology*
  • Endoplasmic Reticulum / virology
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class II / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microsomes / immunology*
  • Microsomes / ultrastructure
  • Microsomes / virology
  • Ovalbumin / immunology*
  • Peptide Fragments / immunology
  • Spleen / cytology
  • Spleen / immunology
  • Vaccinia / prevention & control
  • Viral Vaccines / immunology*
  • Virus Diseases / prevention & control*

Substances

  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • OVA-8
  • Peptide Fragments
  • Viral Vaccines
  • Ovalbumin