Non-mutational neoantigens in disease

[D.ap]

Non-mutational neoantigens in disease

Abstract
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. While 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, the usage of non-canonical initiation codons, alternative RNA splicing, 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.


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11075006/



*https://cureasps.org/forum/viewtopic.php?p=15905#p15905

[laur909]

Non-mutational neoantigens are definitely an important area of study. It's fascinating how immune recognition doesn't always rely on mutations but can come from other mechanisms like epitope mimicry, cryptic epitopes, or even post-translational modifications. These insights could have big implications for understanding disease and designing therapies.