HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Margalit, A. Articles by Gross, G. Search for Related Content PubMed PubMed Citation Articles by Margalit, A. Articles by Gross, G.

Induction of Antitumor Immunity by CTL Epitopes Genetically Linked to Membrane-Anchored ₂-Microglobulin¹

Alon Margalit^2,*,, Helena M. Sheikhet^2,, Yaron Carmi^3,*, Dikla Berko^4,*, Esther Tzehoval, Lea Eisenbach and Gideon Gross^5,*,

^* Laboratory of Immunology, MIGAL-Galilee Technology Center, Kiryat Shmona, Israel; Department of Biotechnology, Tel-Hai Academic College, Upper Galilee, Israel; and Department of Immunology, Weizmann Institute of Science, Rehovot, Israel

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 ₂-microglobulin (₂m) as an integral membrane protein. In this study, we explored membrane-anchored ₂m 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-2K^b binding peptides from MO5, OVA_257–264, and TRP-2_181–188, each genetically fused with the N terminus of membranal ₂m via a short linker. Specific Ab staining and T cell hybridoma activation confirmed that OVA_257–264 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 OVA_257–264/₂m were significantly superior to OVA_257–264-charged cells in their ability to inhibit the growth of pre-established MO5 tumors. Our results highlight the immunotherapeutic potential of membranal ₂m as a universal scaffold for optimizing Ag presentation by MHC-I molecules.