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
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Date
2016-11
Publication Type
Journal Article
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yes
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Abstract
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 were 8–11 amino acids in length and were 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 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.
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published
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Journal / series
Volume
65 (11)
Pages / Article No.
1377 - 1393
Publisher
Springer
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Subject
HLA; Immunocapture; Immunopeptidome; Mass spectrometry; Melanoma; Tumor-associated antigen
Organisational unit
03463 - Neri, Dario (ehemalig) / Neri, Dario (former)
Notes
It was possible to publish this article open access thanks to a Swiss National Licence with the publisher.
Funding
305309 - Profiling Responders In Antibody Therapies (EC)