What makes a neoantigen actually immunogenic?

This open question asks what makes a neoantigen immunogenic: vaccines encode dozens of mutations but only a minority provoke useful T cells, and learning the rules would make vaccines smaller and stronger. Prediction relies on HLA binding and expression, but immunogenicity also depends on TCR repertoire, dissimilarity to self, clonality and dendritic cell presentation (Antigen presentation & immune editing pathway). Long-term responders in the Balachandran pancreatic cohort provide ground truth, and INTerpath-001 follow-up supplies immune-monitoring data. The hypothesis is that a model trained on T-cell responses from trials of Intismeran autogene and other Personalised neoantigen (mRNA) vaccines can cut epitopes per vaccine from 34 to under 10.