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  4. Positional scanning-synthetic peptide library-based analysis of self- and pathogen-derived peptide cross-reactivity with tumor-reactive Melan-A-specific CTL.
 
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Titre

Positional scanning-synthetic peptide library-based analysis of self- and pathogen-derived peptide cross-reactivity with tumor-reactive Melan-A-specific CTL.

Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
The Journal of Immunology  
Auteur(s)
Rubio-Godoy, V.
Auteure/Auteur
Dutoit, V.
Auteure/Auteur
Zhao, Y.
Auteure/Auteur
Simon, R.
Auteure/Auteur
Guillaume, P.
Auteure/Auteur
Houghten, R.
Auteure/Auteur
Romero, P.
Auteure/Auteur
Cerottini, J.C.
Auteure/Auteur
Pinilla, C.
Auteure/Auteur
Valmori, D.
Auteure/Auteur
Liens vers les personnes
Cerottini, Jean-Charles  
Romero, Pedro  
Guillaume, Philippe  
Liens vers les unités
Ludwig Institute for Cancer Research  
ISSN
0022-1767
Statut éditorial
Publié
Date de publication
2002
Volume
169
Numéro
10
Première page
5696
Dernière page/numéro d’article
5707
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Validation Studies
Publication Status: ppublish
Résumé
Synthetic combinatorial peptide libraries in positional scanning format (PS-SCL) have recently emerged as a useful tool for the analysis of T cell recognition. This includes identification of potentially cross-reactive sequences of self or pathogen origin that could be relevant for the understanding of TCR repertoire selection and maintenance, as well as of the cross-reactive potential of Ag-specific immune responses. In this study, we have analyzed the recognition of sequences retrieved by using a biometric analysis of the data generated by screening a PS-SCL with a tumor-reactive CTL clone specific for an immunodominant peptide from the melanocyte differentiation and tumor-associated Ag Melan-A. We found that 39% of the retrieved peptides were recognized by the CTL clone used for PS-SCL screening. The proportion of peptides recognized was higher among those with both high predicted affinity for the HLA-A2 molecule and high predicted stimulatory score. Interestingly, up to 94% of the retrieved peptides were cross-recognized by other Melan-A-specific CTL. Cross-recognition was at least partially focused, as some peptides were cross-recognized by the majority of CTL. Importantly, stimulation of PBMC from melanoma patients with the most frequently recognized peptides elicited the expansion of heterogeneous CD8(+) T cell populations, one fraction of which cross-recognized Melan-A. Together, these results underline the high predictive value of PS-SCL for the identification of sequences cross-recognized by Ag-specific T cells.
Sujets

Antigens, Bacterial/i...

Antigens, Bacterial/m...

Antigens, Neoplasm/im...

Antigens, Neoplasm/me...

Antigens, Viral/immun...

Antigens, Viral/metab...

Autoantigens/immunolo...

Autoantigens/metaboli...

Clone Cells

Combinatorial Chemist...

Cytotoxicity Tests, I...

Cytotoxicity, Immunol...

Epitopes, T-Lymphocyt...

Epitopes, T-Lymphocyt...

HLA-A2 Antigen/metabo...

Humans

Melanoma/immunology

Neoplasm Proteins/imm...

Neoplasm Proteins/met...

Peptide Fragments/ana...

Peptide Fragments/che...

Peptide Library

Protein Binding/immun...

T-Lymphocytes, Cytoto...

T-Lymphocytes, Cytoto...

Tumor Cells, Cultured...

PID Serval
serval:BIB_43BABF091CB4
PMID
12421949
WOS
000179170300042
Permalien
https://iris.unil.ch/handle/iris/41380
Date de création
2008-01-28T10:13:20.745Z
Date de création dans IRIS
2025-05-20T14:02:40Z
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