Abstract:
:Human endogenous retroviruses (HERV) form a substantial part of the human genome, but mostly remain transcriptionally silent under strict epigenetic regulation, yet can potentially be reactivated by malignant transformation or epigenetic therapies. Here, we evaluate the potential for T cell recognition of HERV elements in myeloid malignancies by mapping transcribed HERV genes and generating a library of 1169 potential antigenic HERV-derived peptides predicted for presentation by 4 HLA class I molecules. Using DNA barcode-labeled MHC-I multimers, we find CD8+ T cell populations recognizing 29 HERV-derived peptides representing 18 different HERV loci, of which HERVH-5, HERVW-1, and HERVE-3 have more profound responses; such HERV-specific T cells are present in 17 of the 34 patients, but less frequently in healthy donors. Transcriptomic analyses reveal enhanced transcription of the HERVs in patients; meanwhile DNA-demethylating therapy causes a small and heterogeneous enhancement in HERV transcription without altering T cell recognition. Our study thus uncovers T cell recognition of HERVs in myeloid malignancies, thereby implicating HERVs as potential targets for immunotherapeutic therapies.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Saini SK,Ørskov AD,Bjerregaard AM,Unnikrishnan A,Holmberg-Thydén S,Borch A,Jensen KV,Anande G,Bentzen AK,Marquard AM,Tamhane T,Treppendahl MB,Gang AO,Dufva IH,Szallasi Z,Ternette N,Pedersen AG,Eklund AC,Pimanda J,Grdoi
10.1038/s41467-020-19464-8subject
Has Abstractpub_date
2020-11-09 00:00:00pages
5660issue
1issn
2041-1723pii
10.1038/s41467-020-19464-8journal_volume
11pub_type
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