title: Induction of multiple CD8+ T cell responses against the inducible Hsp70 employing an Hsp70 oligoepitope peptide.
abstract: The inducible heat shock protein Hsp70 has been described as a tumour antigen being frequently overexpressed in tumours of various histologic origins, with a role in tumourigenicity, as a critical event in tumour progression. A strategy to enhance the immune response to an antigen is the identification of multiple epitopes and the induction of a polyspecific response. Applied to tumour vaccination, such a polyspecific response should lead to a more robust antitumour efficacy. The long peptide Hsp70380-402 encompasses three nonamer peptides with a high affinity for HLA-A *0201. In a previous paper, we have shown that two of these nonamer peptides, p391 and p393, can raise CTL to recognize tumour cells overexpressing Hsp70. In the present paper, we demonstrate that the third nonamer peptide, p380, is a new epitope efficient in raising an antitumour immune response. The p380-402 polypeptide was able to induce an immune response against each of the three constituent epitopes both in vivo in HLA-A *0201 transgenic mice and in vitro with human PBMC. This polypeptide therefore constitutes an interesting candidate for the induction of multiple HLA-A *0201-restricted anti-Hsp70 antitumour CTL responses.
authors.affiliation: INSERM U487, Institut Gustave Roussy, 94805 Villejuif, France. ofaure@idm-biotech.com
authors.forename: Olivier
authors.initials: O
authors.lastname: Faure
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Graff-Dubois
authors.forename: Pedro M S
authors.initials: PM
authors.lastname: Alves
authors.forename: Sébastien
authors.initials: S
authors.lastname: Cornet
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Duffour
authors.forename: Antonio
authors.initials: A
authors.lastname: Scardino
authors.forename: David-Alexandre
authors.initials: DA
authors.lastname: Gross
authors.forename: Isabelle
authors.initials: I
authors.lastname: Miconnet
authors.forename: Margarita
authors.initials: M
authors.lastname: Salcedo
authors.forename: Salem
authors.initials: S
authors.lastname: Chouaib
authors.forename: François A
authors.initials: FA
authors.lastname: Lemonnier
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Abastado
authors.forename: Kostas
authors.initials: K
authors.lastname: Kosmatopoulos
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000737:chemistry / Q000276:immunology*; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019556:COS Cells; D002522:Chlorocebus aethiops; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D015234:HLA-A Antigens / Q000276:immunology; D015789:HLA-A2 Antigen; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D014162:Transfection
chemical_list: D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D018840:HSP70 Heat-Shock Proteins; D010455:Peptides