Titre
Spontaneous CD8 T cell responses against the melanocyte differentiation antigen RAB38/NY-MEL-1 in melanoma patients
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Walton, S. M.
Auteure/Auteur
Gerlinger, M.
Auteure/Auteur
de la Rosa, O.
Auteure/Auteur
Nuber, N.
Auteure/Auteur
Knights, A.
Auteure/Auteur
Gati, A.
Auteure/Auteur
Laumer, M.
Auteure/Auteur
Strauss, L.
Auteure/Auteur
Exner, C.
Auteure/Auteur
Schafer, N.
Auteure/Auteur
Urosevic, M.
Auteure/Auteur
Dummer, R.
Auteure/Auteur
Tiercy, J. M.
Auteure/Auteur
Mackensen, A.
Auteure/Auteur
Jaeger, E.
Auteure/Auteur
Levy, F.
Auteure/Auteur
Knuth, A.
Auteure/Auteur
Jager, D.
Auteure/Auteur
Zippelius, A.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
0022-1767
Statut éditorial
Publié
Date de publication
2006-12
Volume
177
Numéro
11
Première page
8212
Dernière page/numéro d’article
8
Peer-reviewed
Oui
Langue
anglais
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Dec 1
Research Support, Non-U.S. Gov't --- Old month value: Dec 1
Résumé
The melanocyte differentiation Ag RAB38/NY-MEL-1 was identified by serological expression cloning (SEREX) and is expressed in the vast majority of melanoma lesions. The immunogenicity of RAB38/NY-MEL-1 has been corroborated previously by the frequent occurrence of specific Ab responses in melanoma patients. To elucidate potential CD8 T cell responses, we applied in vitro sensitization with overlapping peptides spanning the RAB38/NY-MEL-1 protein sequence and the reverse immunology approach. The identified peptide RAB38/NY-MEL-1(50-58) exhibited a marked response in ELISPOT assays after in vitro sensitization of CD8 T cells from HLA-A *0201(+) melanoma patients. In vitro digestion assays using purified proteasomes provided evidence of natural processing of RAB38/NY-MEL-1(50-58) peptide. Accordingly, monoclonal RAB38/NY-MEL-1(50-58)-specific T cell populations were capable of specifically recognizing HLA-A2(+) melanoma cell lines expressing RAB38/NY-MEL-1. Applying fluorescent HLA-A2/RAB38/NY-MEL-1(50-58) multimeric constructs, we were able to document a spontaneously developed memory/effector CD8 T cell response against this peptide in a melanoma patient. To elucidate the Ag-processing pathway, we demonstrate that RAB38/NY-MEL-1(50-58) is produced efficiently by the standard proteasome and the immunoproteasome. In addition to the identification of a RAB38/NY-MEL-1-derived immunogenic CD8 T cell epitope, this study is instrumental for both the onset and monitoring of future RAB38/NY-MEL-1-based vaccination trials.
Sujets
PID Serval
serval:BIB_D1FA2EC7EDBE
PMID
Date de création
2008-01-28T10:17:31.520Z
Date de création dans IRIS
2025-05-20T23:21:20Z