NDLI: 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.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Chevaleyre, Claire Hans, Stephane Maillère, Bernard Benhamouda, Nadine Bats, Anne-Sophie Le Pimpec-Barthes, Françoise Mhoumadi, Anais Vinatier, Emeline Nozach, Hervé Castelli, Florence A. Favry, Emmanuel Marcon, Elodie Tartour, Eric Cosler, Guillaume Fabre, Elizabeth Oudard, Stephane
Description	Author Affiliation: Chevaleyre C ( 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); Benhamouda N ( INSERM U970, Paris Centre de Recherche Cardiovasculaire Université Paris Descartes Sorbonne Paris Cité, Service d'Immunologie Biologique, Hopital Européen Georges Pompidou, Paris 75015, France); Favry E ( 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); Fabre E ( Service d'Oncologie Médicale, Hopital Européen Georges Pompidou, Paris 75015, France); Mhoumadi A ( 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); Nozach H ( 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); Marcon E ( 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); Cosler G ( INSERM U970, Paris Centre de Recherche Cardiovasculaire Université Paris Descartes Sorbonne Paris Cité, Service d'Immunologie Biologique, Hopital Européen Georges Pompidou, Paris 75015, France); Vinatier E ( INSERM U970, Paris Centre de Recherche Cardiovasculaire Université Paris Descartes Sorbonne Paris Cité, Service d'Immunologie Biologique, Hopital Européen Georges Pompidou, Paris 75015, France); Oudard S ( Service d'Oncologie Médicale, Hopital Européen Georges Pompidou, Paris 75015, France); Hans S ( Service d'Otorhinolaryngologie, Hopital Européen Georges Pompidou, Paris 75015, France); Le Pimpec-Barthes F ( Service de Chirurgie Thoracique et Transplantation Pulmonaire, Hopital Européen Georges Pompidou, Paris 75015, France); Bats AS ( Chirurgie Cancérologique Gynécologique et du Sein, Hopital Européen Georges Pompidou, Paris 75015, France.); Castelli FA ( 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); Tartour E ( INSERM U970, Paris Centre de Recherche Cardiovasculaire Université Paris Descartes Sorbonne Paris Cité, Service d'Immunologie Biologique, Hopital Européen Georges Pompidou, Paris 75015, France); Maillère B ( 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)
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.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	4
Volume Number	195
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2015-08-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Cd4-positive T-lymphocytes Immunology Cyclin B1 Epitopes, T-lymphocyte Immunologic Memory Neoplasms Antibodies Case-control Studies Cell Line Metabolism Histocompatibility Antigens Class Ii Immunodominant Epitopes Immunoglobulin G Peptides Protein Binding T-cell Antigen Receptor Specificity Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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