Englander Institute for Precision Medicine

Non-mutational neoantigens in disease.

TitleNon-mutational neoantigens in disease.
Publication TypeJournal Article
Year of Publication2024
AuthorsStern LJ, Clement C, Galluzzi L, Santambrogio L
JournalNat Immunol
Date Published2024 Jan
KeywordsAnimals, Antigens, Epitopes, Humans, Mammals, Peptides, T-Lymphocytes

The ability of mammals to mount adaptive immune responses culminating with the establishment of immunological memory is predicated on the ability of the mature T cell repertoire to recognize antigenic peptides presented by syngeneic MHC class I and II molecules. Although it is widely believed that mature T cells are highly skewed towards the recognition of antigenic peptides originating from genetically diverse (for example, foreign or mutated) protein-coding regions, preclinical and clinical data rather demonstrate that novel antigenic determinants efficiently recognized by mature T cells can emerge from a variety of non-mutational mechanisms. In this Review, we describe various mechanisms that underlie the formation of bona fide non-mutational neoantigens, such as epitope mimicry, upregulation of cryptic epitopes, usage of non-canonical initiation codons, alternative RNA splicing, and defective ribosomal RNA processing, as well as both enzymatic and non-enzymatic post-translational protein modifications. Moreover, we discuss the implications of the immune recognition of non-mutational neoantigens for human disease.

Alternate JournalNat Immunol
PubMed ID38168954
PubMed Central ID4757912
Grant ListP01 AG031782 / AG / NIA NIH HHS / United States

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