Walton, Senta M. and Gerlinger, Marco and de la Rosa, Olga and Nuber, Natko and Knights, Ashley and Gati, Asma and Laumer, Monika and Strauss, Laura and Exner, Carolin and Schaefer, Niklaus and Urosevic, Mirjana and Dununer, Reinhard and Tiercy, Jean-Marie and Mackensen, Andreas and Jaeger, Elke and Levy, Frederic and Knuth, Alexander and Jaeger, Dirk and Zippelius, Alfred (2006) Spontaneous CD8 T cell responses against the melanocyte differentiation antigen RAB38/NY-MEL-1 in melanoma patients. JOURNAL OF IMMUNOLOGY, 177 (11). pp. 8212-8218. ISSN 0022-1767,
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | METASTATIC MELANOMA; ANTIBODY-RESPONSES; HLA-A2 MELANOMAS; DENDRITIC CELLS; LYMPHOCYTES; PEPTIDE; PROTEASOME; IDENTIFICATION; IMMUNOTHERAPY; NY-ESO-1; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 18 Jan 2021 09:17 |
| Last Modified: | 18 Jan 2021 09:17 |
| URI: | https://pred.uni-regensburg.de/id/eprint/33702 |
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