Non-traditionally derived CTL epitopes: exceptions that prove the rules?

Recent data indicate that cytotoxic T lymphocyte (CTL) epitopes in viral, tumor and model systems are encoded by non-primary open reading frame (ORF) sequences, as well as other non-traditional sources. Here, Shawn-Marie Mayrand and William Green review these findings and discuss whether these non-traditionally derived CTL epitopes influence the shaping of the T-cell repertoire and immune regulation.