title: The Tumor Antigen Cyclin B1 Hosts Multiple CD4 T Cell Epitopes Differently Recognized by Pre-Existing Naive and Memory Cells in Both Healthy and Cancer Donors.
abstract: Cyclin B1 (CCNB1) is considered as a potential target for a cancer vaccine, as it is overexpressed in many malignant cells, while being transiently expressed in normal cells. To evaluate the CD4 T cell response to CCNB1, we derived T cell lines by multiple weekly rounds of stimulation with recombinant CCNB1 of T cells collected in healthy donors (long-term T cell assays). T cell lines were specific for 15 immunodominant peptides and derived preferentially from naive T cells. From 74 overlapping peptides, 20 peptides were selected for their broad specificity of binding to HLA class II molecules and included most of the immunodominant epitopes. They primed in vitro a large number of specific CD4 T cell lines in all the donors. Immunodominant epitopes were the most efficacious in long-term T cell assays, both in terms of number of specific T cell lines and number of responding donors. The 20 peptides were also submitted to short-term T cell assays using cells collected in healthy and cancer patients with the aim to evaluate the memory response. The recognized peptides differed from the immunodominant peptides and were part of the best promiscuous peptides. We also observed pre-existing CCNB1-specifc IgG Abs in both healthy and cancer donors. Long- and short-term T cell assays revealed that CCNB1 contained many CD4 T cell epitopes, which are differentially recognized by pre-existing naive and memory CD4 T cells. These observations are of value for the design of cancer vaccines.
authors.affiliation: Commissariat à l'Energie Atomique, Institut de Biologie et de Technologies, Service d'Ingénierie Moléculaire des Protéines, Laboratoire d'Excellence en Recherche sur le Médicament et l'Innovation Thérapeutique, Laboratoire d'Excellence Institut de Recherche Vaccinal, Gif Sur Yvette F-91191, France;
authors.forename: Claire
authors.initials: C
authors.lastname: Chevaleyre
authors.affiliation: INSERM U970, Paris Centre de Recherche Cardiovasculaire Université Paris Descartes Sorbonne Paris Cité, Service d'Immunologie Biologique, Hopital Européen Georges Pompidou, Paris 75015, France;
authors.forename: Nadine
authors.initials: N
authors.lastname: Benhamouda
authors.affiliation: Commissariat à l'Energie Atomique, Institut de Biologie et de Technologies, Service d'Ingénierie Moléculaire des Protéines, Laboratoire d'Excellence en Recherche sur le Médicament et l'Innovation Thérapeutique, Laboratoire d'Excellence Institut de Recherche Vaccinal, Gif Sur Yvette F-91191, France;
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Favry
authors.affiliation: Service d'Oncologie Médicale, Hopital Européen Georges Pompidou, Paris 75015, France;
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Fabre
authors.affiliation: Commissariat à l'Energie Atomique, Institut de Biologie et de Technologies, Service d'Ingénierie Moléculaire des Protéines, Laboratoire d'Excellence en Recherche sur le Médicament et l'Innovation Thérapeutique, Laboratoire d'Excellence Institut de Recherche Vaccinal, Gif Sur Yvette F-91191, France;
authors.forename: Anais
authors.initials: A
authors.lastname: Mhoumadi
authors.affiliation: Commissariat à l'Energie Atomique, Institut de Biologie et de Technologies, Service d'Ingénierie Moléculaire des Protéines, Laboratoire d'Excellence en Recherche sur le Médicament et l'Innovation Thérapeutique, Laboratoire d'Excellence Institut de Recherche Vaccinal, Gif Sur Yvette F-91191, France;
authors.forename: Hervé
authors.initials: H
authors.lastname: Nozach
authors.affiliation: Commissariat à l'Energie Atomique, Institut de Biologie et de Technologies, Service d'Ingénierie Moléculaire des Protéines, Laboratoire d'Excellence en Recherche sur le Médicament et l'Innovation Thérapeutique, Laboratoire d'Excellence Institut de Recherche Vaccinal, Gif Sur Yvette F-91191, France;
authors.forename: Elodie
authors.initials: E
authors.lastname: Marcon
authors.affiliation: INSERM U970, Paris Centre de Recherche Cardiovasculaire Université Paris Descartes Sorbonne Paris Cité, Service d'Immunologie Biologique, Hopital Européen Georges Pompidou, Paris 75015, France;
authors.forename: Guillaume
authors.initials: G
authors.lastname: Cosler
authors.affiliation: INSERM U970, Paris Centre de Recherche Cardiovasculaire Université Paris Descartes Sorbonne Paris Cité, Service d'Immunologie Biologique, Hopital Européen Georges Pompidou, Paris 75015, France;
authors.forename: Emeline
authors.initials: E
authors.lastname: Vinatier
authors.affiliation: Service d'Oncologie Médicale, Hopital Européen Georges Pompidou, Paris 75015, France;
authors.forename: Stephane
authors.initials: S
authors.lastname: Oudard
authors.affiliation: Service d'Otorhinolaryngologie, Hopital Européen Georges Pompidou, Paris 75015, France;
authors.forename: Stephane
authors.initials: S
authors.lastname: Hans
authors.affiliation: Service de Chirurgie Thoracique et Transplantation Pulmonaire, Hopital Européen Georges Pompidou, Paris 75015, France; and.
authors.forename: Françoise
authors.initials: F
authors.lastname: Le Pimpec-Barthes
authors.affiliation: Chirurgie Cancérologique Gynécologique et du Sein, Hopital Européen Georges Pompidou, Paris 75015, France.
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Bats
authors.affiliation: Commissariat à l'Energie Atomique, Institut de Biologie et de Technologies, Service d'Ingénierie Moléculaire des Protéines, Laboratoire d'Excellence en Recherche sur le Médicament et l'Innovation Thérapeutique, Laboratoire d'Excellence Institut de Recherche Vaccinal, Gif Sur Yvette F-91191, France;
authors.forename: Florence A
authors.initials: FA
authors.lastname: Castelli
authors.affiliation: INSERM U970, Paris Centre de Recherche Cardiovasculaire Université Paris Descartes Sorbonne Paris Cité, Service d'Immunologie Biologique, Hopital Européen Georges Pompidou, Paris 75015, France;
authors.forename: Eric
authors.initials: E
authors.lastname: Tartour
authors.affiliation: Commissariat à l'Energie Atomique, Institut de Biologie et de Technologies, Service d'Ingénierie Moléculaire des Protéines, Laboratoire d'Excellence en Recherche sur le Médicament et l'Innovation Thérapeutique, Laboratoire d'Excellence Institut de Recherche Vaccinal, Gif Sur Yvette F-91191, France; Service d'Otorhinolaryngologie, Hopital Européen Georges Pompidou, Paris 75015, France; bernard.maillere@cea.fr.
authors.forename: Bernard
authors.initials: B
authors.lastname: Maillère
mesh_terms: D000906:Antibodies / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D002460:Cell Line; D056744:Cyclin B1 / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007156:Immunologic Memory; D009369:Neoplasms / Q000276:immunology*; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology
chemical_list: D000906:Antibodies; D056744:Cyclin B1; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D016056:Immunodominant Epitopes; D007074:Immunoglobulin G; D010455:Peptides