Priority Research Papers:
Use of HLA peptidomics and whole exome sequencing to identify human immunogenic neo-antigens
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Shelly Kalaora1, Eilon Barnea2,*, Efrat Merhavi-Shoham3,*, Nouar Qutob1, Jamie K. Teer4, Nilly Shimony3, Jacob Schachter3, Steven A. Rosenberg5, Michal J. Besser3,6,**, Arie Admon2,** and Yardena Samuels1
1 Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
2 Department of Biology, Technion, Haifa, Israel
3 The Ella Lemelbaum Institute for Melanoma, Chaim Sheba Medical Center, Tel Hashomer, Israel
4 Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
5 National Cancer Institute, NIH, MD, USA
6 Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
* These authors have contributed equally to this work
** These authors have contributed equally to this work
Yardena Samuels, email:
Keywords: HLA, TILs
Received: November 26, 2015 Accepted: December 30, 2015 Published: January 20, 2016
The antigenicity of cells is demarcated by the peptides bound by their Human Leucocyte Antigen (HLA) molecules. Through this antigen presentation, T cell specificity response is controlled. As a fraction of the expressed mutated peptides is presented on the HLA, these neo-epitopes could be immunogenic. Such neo-antigens have recently been identified through screening for predicted mutated peptides, using synthetic peptides or ones expressed from minigenes, combined with screening of patient tumor-infiltrating lymphocytes (TILs). Here we present a time and cost-effective method that combines whole-exome sequencing analysis with HLA peptidome mass spectrometry, to identify neo-antigens in a melanoma patient. Of the 1,019 amino acid changes identified through exome sequencing, two were confirmed by mass spectrometry to be presented by the cells. We then synthesized peptides and evaluated the two mutated neo-antigens for reactivity with autologous bulk TILs, and found that one yielded mutant-specific T-cell response. Our results demonstrate that this method can be used for immune response prediction and promise to provide an alternative approach for identifying immunogenic neo-epitopes in cancer.
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