Chimeric MHC class I- and II-restricted non-self epitopes broaden antitumor T cell reactions.

ABSTRACT: The mechanism by which one non-self antigen augments T cell immune responses to another remains unclear. We found that these expanded immune responses could derive from chimeric non-self peptides. These peptides, which we termed complete T cell antigens (CTAs), must be expressed intracellularly as single-chain chimeras containing both MHC class I- and II-restricted epitopes. CTAs, even unrelated to tumor antigens, when administered as live cell adjuvants or in cDNA-transfected muscle, increased T cell reactivity against tumor neoantigens. Mechanistically, CTA treatment altered dendritic cell phenotype in a CD4+ T cell-dependent manner, suppressing CD8+ T cell exhaustion and generating self-renewing CD8+ T cells in tumors. Cancers predicted to have long non-self peptides resulting from fram

SUBMITTER: Zhang R 

PROVIDER: S-EPMC12679993 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature