Spontaneous CD8 T cell responses against the melanocyte differentiation antigen RAB38/NY-MEL-1 in melanoma patients

Details

Serval ID
serval:BIB_D1FA2EC7EDBE
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Spontaneous CD8 T cell responses against the melanocyte differentiation antigen RAB38/NY-MEL-1 in melanoma patients
Journal
Journal of Immunology
Author(s)
Walton  S. M., Gerlinger  M., de la Rosa  O., Nuber  N., Knights  A., Gati  A., Laumer  M., Strauss  L., Exner  C., Schafer  N., Urosevic  M., Dummer  R., Tiercy  J. M., Mackensen  A., Jaeger  E., Levy  F., Knuth  A., Jager  D., Zippelius  A.
ISSN
0022-1767 (Print)
Publication state
Published
Issued date
12/2006
Volume
177
Number
11
Pages
8212-8
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Dec 1
Abstract
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.
Keywords
Antigen Presentation/immunology Antigens, Neoplasm/*immunology Blotting, Western CD8-Positive T-Lymphocytes/*immunology Cells, Cultured Epitopes, T-Lymphocyte/immunology Flow Cytometry Fluorescent Antibody Technique Humans Melanoma/*immunology Reverse Transcriptase Polymerase Chain Reaction Transfection rab GTP-Binding Proteins/*immunology
Pubmed
Web of science
Create date
28/01/2008 11:17
Last modification date
20/08/2019 15:52
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