Mass spectrometric analysis of the HLA class I peptidome of melanoma cell lines as a promising tool for the identification of putative tumor-associated HLA epitopes

Autor: Andreas Gloger, Danilo Ritz, Dario Neri, Tim Fugmann
Rok vydání: 2016
Předmět:
Zdroj: Cancer Immunology, Immunotherapy
Cancer Immunology Immunotherapy
ISSN: 0340-7004
DOI: 10.1007/s00262-016-1897-3
Popis: Melanoma is one of the most immunogenic tumors and extensive lists of potential tumor rejection antigens have been collected during the last decades. By isolating human leukocyte antigen (HLA) class I complexes from five melanoma cell lines (FM-82, FM-93/2, Mel-624, MeWo and SK-Mel-5) and sequencing HLA-eluted peptides by mass spectrometry, we identified over 10’000 unique peptides with high confidence. The majority of the peptides was 8 to 11 amino acids in length and was predicted to bind to the respective HLA alleles. Over 250 epitopes, corresponding to previously described tumor-associated antigens, were identified, suggesting that HLA peptidome analysis may facilitate the characterization of putative tumor rejection antigens. MeWo and SK-Mel-5 cell lines were further interrogated for neo-epitopes, revealing one peptide from MeWo cells carrying an amino acid mutation. We also observed a remarkable overlap between A*03:01 peptides eluted from Mel-624 cells and A*03:01 peptides recovered from soluble HLA (sHLA) complexes purified from two melanoma patients, shedding light on the similarity of the HLA peptidome in cell lines and in patient-derived material. The reliable characterization of the HLA class I peptidome in melanoma promises to facilitate the identification of tumor rejection antigens and the development of immunotherapeutic strategies.
Databáze: OpenAIRE