Induction of antitumor immunity by CTL epitopes genetically linked to membrane-anchored beta2-microglobulin.
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.
Margalit
Alon
A
Laboratory of Immunology, MIGAL-Galilee Technology Center, Kiryat Shmona, Israel.
Sheikhet
Helena M
HM
Carmi
Yaron
Y
Berko
Dikla
D
Tzehoval
Esther
E
Eisenbach
Lea
L
Gross
Gideon
G
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology*; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005434:Flow Cytometry; D006183:H-2 Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D008546:Melanoma, Experimental / Q000276:immunology*; D051379:Mice; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D001613:beta 2-Microglobulin / Q000737:chemistry / Q000235:genetics / Q000276:immunology*
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D001613:beta 2-Microglobulin