Identification of Glycopeptides as Posttranslationally Modified Neoantigens in Leukemia

Stacy A Malaker, Sarah A Penny, Lora G Steadman, Paisley T Myers, Justin C Loke, Manoj Raghavan, Dina L Bai, Jeffrey Shabanowitz, Donald F Hunt, Mark Cobbold

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)
208 Downloads (Pure)

Abstract

Leukemias are highly immunogenic, but they have a low mutational load, providing few mutated peptide targets. Thus, the identification of alternative neoantigens is a pressing need. Here, we identify 36 MHC class I-associated peptide antigens with O-linked β-N-acetylglucosamine (O-GlcNAc) modifications as candidate neoantigens, using three experimental approaches. Thirteen of these peptides were also detected with disaccharide units on the same residues and two contain either mono- and/or di-methylated arginine residues. A subset were linked with key cancer pathways, and these peptides were shared across all of the leukemia patient samples tested (5/5). Seven of the O-GlcNAc peptides were synthesized and five (71%) were shown to be associated with multifunctional memory T-cell responses in healthy donors. An O-GlcNAc-specific T-cell line specifically killed autologous cells pulsed with the modified peptide, but not the equivalent unmodified peptide. Therefore, these posttranslationally modified neoantigens provide logical targets for cancer immunotherapy. Cancer Immunol Res; 5(5); 376-84. ©2017 AACR.

Original languageEnglish
Pages (from-to)376-384
Number of pages9
JournalCancer immunology research
Volume5
Issue number5
Early online date17 Mar 2017
DOIs
Publication statusPublished - May 2017

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