Use of HLA peptidomics and whole exome sequencing to identify human immunogenic neo-antigens

Shelly Kalaora, Eilon Barnea, Efrat Merhavi-Shoham, Nouar Qutob, Jamie K. Teer, Nilly Shimony, Jacob Schachter, Steven A. Rosenberg, Michal J. Besser, Arie Admon, Yardena Samuels

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5110-5117
Number of pages8
JournalOncotarget
Volume7
Issue number5
DOIs
StatePublished - 2016

Keywords

  • HLA
  • TILs

ASJC Scopus subject areas

  • Oncology

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    Kalaora, S., Barnea, E., Merhavi-Shoham, E., Qutob, N., Teer, J. K., Shimony, N., Schachter, J., Rosenberg, S. A., Besser, M. J., Admon, A., & Samuels, Y. (2016). Use of HLA peptidomics and whole exome sequencing to identify human immunogenic neo-antigens. Oncotarget, 7(5), 5110-5117. https://doi.org/10.18632/oncotarget.6960