Induction of antitumor immunity by CTL epitopes genetically linked to membrane-anchored beta2-microglobulin

J Immunol. 2006 Jan 1;176(1):217-24. doi: 10.4049/jimmunol.176.1.217.

Abstract

Level and persistence of antigenic peptides presented by APCs on MHC class I (MHC-I) molecules influence the magnitude and quality of the ensuing CTL response. We recently demonstrated the unique immunological properties conferred on APCs by expressing beta2-microglobulin (beta2m) as an integral membrane protein. In this study, we explored membrane-anchored beta2m as a platform for cancer vaccines using as a model MO5, an OVA-expressing mouse B16 melanoma. We expressed in mouse RMA-S cells two H-2Kb binding peptides from MO5, OVA257-264, and TRP-2181-188, each genetically fused with the N terminus of membranal beta2m via a short linker. Specific Ab staining and T cell hybridoma activation confirmed that OVA257-264 was properly situated in the MHC-I binding groove. In vivo, transfectants expressing both peptides elicited stronger CTLs and conferred better protection against MO5 than peptide-saturated RMA-S cells. Cells expressing OVA257-264/beta2m were significantly superior to OVA257-264-charged cells in their ability to inhibit the growth of pre-established MO5 tumors. Our results highlight the immunotherapeutic potential of membranal beta2m as a universal scaffold for optimizing Ag presentation by MHC-I molecules.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / immunology
  • Antigens, Neoplasm / immunology
  • Cancer Vaccines / immunology*
  • Cell Membrane / immunology
  • Cell Membrane / metabolism
  • Epitopes, T-Lymphocyte / immunology*
  • Flow Cytometry
  • H-2 Antigens / chemistry
  • H-2 Antigens / genetics
  • H-2 Antigens / immunology
  • Melanoma, Experimental / immunology*
  • Mice
  • T-Lymphocytes, Cytotoxic / immunology*
  • Transfection
  • beta 2-Microglobulin / chemistry
  • beta 2-Microglobulin / genetics
  • beta 2-Microglobulin / immunology*

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines
  • Epitopes, T-Lymphocyte
  • H-2 Antigens
  • H-2Kb protein, mouse
  • beta 2-Microglobulin