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
Claire Chevaleyre
(1)
,
Nadine Benhamouda
(2)
,
Emmanuel Favry
(1)
,
Elizabeth Fabre
,
Anais Mhoumadi
(1)
,
Hervé Nozach
(1)
,
Elodie Marcon
(1)
,
Guillaume Cosler
,
Emeline Vinatier
,
Stephane Oudard
,
Stephane Hans
(3, 4)
,
Françoise Le Pimpec-Barthes
,
Anne-Sophie Bats
,
Florence A. Castelli
(5, 6, 7, 8, 9, 10, 11)
,
Eric Tartour
,
Bernard Maillere
1
IBITECS -
Institut de Biologie et de Technologies de Saclay
2 PARCC - UMR-S U970 - Paris-Centre de Recherche Cardiovasculaire
3 LPP - LPP - Laboratoire de Phonétique et Phonologie - UMR 7018
4 Service d'oto-rhino-laryngologie et chirurgie cervico-faciale [CHU HEGP]
5 MTS - Médicaments et Technologies pour la Santé
6 SPI - Service de Pharmacologie et Immunoanalyse
7 LI-MS - Laboratoire Innovations en Spectrométrie de Masse pour la santé
8 SMART-OMICS - Small molecule analysis and omics
9 CEA - CEA- Saclay
10 Université Paris-Saclay
11 MetaboHUB-IDF
2 PARCC - UMR-S U970 - Paris-Centre de Recherche Cardiovasculaire
3 LPP - LPP - Laboratoire de Phonétique et Phonologie - UMR 7018
4 Service d'oto-rhino-laryngologie et chirurgie cervico-faciale [CHU HEGP]
5 MTS - Médicaments et Technologies pour la Santé
6 SPI - Service de Pharmacologie et Immunoanalyse
7 LI-MS - Laboratoire Innovations en Spectrométrie de Masse pour la santé
8 SMART-OMICS - Small molecule analysis and omics
9 CEA - CEA- Saclay
10 Université Paris-Saclay
11 MetaboHUB-IDF
Claire Chevaleyre
- Fonction : Auteur
- PersonId : 1202787
Elizabeth Fabre
- Fonction : Auteur
Elodie Marcon
- Fonction : Auteur
- PersonId : 780926
- ORCID : 0000-0002-5018-6312
Guillaume Cosler
- Fonction : Auteur
Emeline Vinatier
- Fonction : Auteur
Stephane Oudard
- Fonction : Auteur
- PersonId : 764763
- ORCID : 0000-0003-0893-285X
Françoise Le Pimpec-Barthes
- Fonction : Auteur
Anne-Sophie Bats
- Fonction : Auteur
Florence A. Castelli
- Fonction : Auteur
- PersonId : 1326713
- IdHAL : florence-castelli
- ORCID : 0000-0002-6886-8549
Eric Tartour
- Fonction : Auteur
- PersonId : 762312
- ORCID : 0000-0002-7323-468X
- IdRef : 076543234
Bernard Maillere
- Fonction : Auteur
- PersonId : 1337238
- IdHAL : bernard-maillere
- ORCID : 0000-0001-5580-4194
Résumé
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.
Domaines
LinguistiqueFormat du dépôt | Notice |
---|---|
Type de dépôt | Article dans une revue |
Titre |
en
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
|
Résumé |
en
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.
|
Auteur(s) |
Claire Chevaleyre
1
, Nadine Benhamouda
2
, Emmanuel Favry
1
, Elizabeth Fabre
, Anais Mhoumadi
1
, Hervé Nozach
1
, Elodie Marcon
1
, Guillaume Cosler
, Emeline Vinatier
, Stephane Oudard
, Stephane Hans
3, 4
, Françoise Le Pimpec-Barthes
, Anne-Sophie Bats
, Florence A. Castelli
5, 6, 7, 8, 9, 10, 11
, Eric Tartour
, Bernard Maillere
1
IBITECS -
Institut de Biologie et de Technologies de Saclay
( 40438 )
- CEA Saclay bat 532 91191 Gif sur Yvette cedex
- France
2
PARCC - UMR-S U970 -
Paris-Centre de Recherche Cardiovasculaire
( 81503 )
- 56 rue Leblanc
75015 PARIS
FRANCE
- France
3
LPP -
LPP - Laboratoire de Phonétique et Phonologie - UMR 7018
( 986 )
- Université Sorbonne Nouvelle
Maison de la Recherche
4, rue des Irlandais
75005 PARIS
- France
4
Service d'oto-rhino-laryngologie et chirurgie cervico-faciale [CHU HEGP]
( 25104 )
- Hôpital Européen Georges Pompidou
20, rue Leblanc 75908 Paris
- France
5
MTS -
Médicaments et Technologies pour la Santé
( 531263 )
- CEA
- SPI
- Bât. 136 Saclay 91191 GIF-SUR-YVETTE
- France
6
SPI -
Service de Pharmacologie et Immunoanalyse
( 40494 )
- France
7
LI-MS -
Laboratoire Innovations en Spectrométrie de Masse pour la santé
( 1158713 )
- Laboratory of innovations in mass spectrometry for health
- France
8
SMART-OMICS -
Small molecule analysis and omics
( 1158714 )
- France
9
CEA -
CEA- Saclay
( 20287 )
- CEA-Saclay Service de Physique Nucléaire 91191 Gif-sur-Yvette
- France
10
Université Paris-Saclay
( 419361 )
- Bâtiment Bréguet, 3 Rue Joliot Curie 2e ét, 91190 Gif-sur-Yvette
- France
11
MetaboHUB-IDF
( 1076048 )
- CEA-Saclay, 91191 Gif-sur-Yvette
- France
|
Langue du document |
Anglais
|
Nom de la revue |
|
Vulgarisation |
Non
|
Comité de lecture |
Oui
|
Audience |
Internationale
|
Date de publication |
2015
|
Volume |
195
|
Numéro |
4
|
Page/Identifiant |
1891-1901
|
Domaine(s) |
|
Mots-clés |
en
Cancer Donors, Memory Cells
|
DOI | 10.4049/jimmunol.1402548 |
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