MHC II immunogenicity shapes the neoepitope landscape in human tumors
- Authors
- Kim, Jeong Yeon; Cha, Hongui; Kim, Kyeonghui; Sung, Changhwan; An, Jinhyeon; Bang, Hyoeun; Kim, Hyungjoo; Yang, Jin Ok; Chang, Suhwan; Shin, Incheol; Noh, Seung-Jae; Shin, Inkyung; Cho, Dae-Yeon; Lee, Se-Hoon; Choi, Jung Kyoon
- Issue Date
- Feb-2023
- Publisher
- NATURE PORTFOLIO
- Citation
- NATURE GENETICS, v.55, no.2, pp.221 - 231
- Indexed
- SCIE
SCOPUS
- Journal Title
- NATURE GENETICS
- Volume
- 55
- Number
- 2
- Start Page
- 221
- End Page
- 231
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/185081
- DOI
- 10.1038/s41588-022-01273-y
- ISSN
- 1061-4036
- Abstract
- Despite advances in predicting physical peptide-major histocompatibility complex I (pMHC I) binding, it remains challenging to identify functionally immunogenic neoepitopes, especially for MHC II. By using the results of > 36,000 immunogenicity assay, we developed a method to identify pMHC whose structural alignment facilitates T cell reaction. Our method predicted neoepitopes for MHC II and MHC I that were responsive to checkpoint blockade when applied to > 1,200 samples of various tumor types. To investigate selection by spontaneous immunity at the single epitope level, we analyzed the frequency spectrum of > 25 million mutations in > 9,000 treatment-naive tumors with > 100 immune phenotypes. MHC II immunogenicity specifically lowered variant frequencies in tumors under high immune pressure, particularly with high TCR clonality and MHC II expression. A similar trend was shown for MHC I neoepitopes, but only in particular tissue types. In summary, we report immune selection imposed by MHC II-restricted natural or therapeutic T cell reactivity.
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