Non-mutational neoantigens in disease

Area of Science:

• Immunology
• Molecular Biology

Background:

• Adaptive immunity relies on T cells recognizing peptides presented by MHC molecules.
• T cell recognition is traditionally thought to focus on mutated or foreign antigens.
• Emerging evidence suggests non-mutational mechanisms also generate T cell-recognized antigens.

Purpose of the Study:

• To review mechanisms generating non-mutational neoantigens.
• To discuss the implications of non-mutational neoantigen recognition in human disease.

Main Methods:

• Literature review of preclinical and clinical data.
• Analysis of various molecular and cellular processes.

Main Results:

• Non-mutational neoantigens arise from epitope mimicry, cryptic epitopes, non-canonical translation, RNA splicing, ribosomal processing errors, and post-translational modifications.
• These neoantigens are efficiently recognized by mature T cells.

Conclusions:

• The repertoire of antigens recognized by T cells is broader than previously assumed.
• Non-mutational neoantigens play a significant role in immune responses and human diseases.