A natural cytotoxic T cell response in a spontaneously regressing human melanoma targets a neoantigen resulting from a somatic point mutation

We have studied a case of human primary melanoma displaying the classical s igns of a spontaneous regression in order to characterize potentially effic ient anti-tumor T cell responses. in a previous series of experiments a uni que TCR V beta 16(+) T cell was shown to be highly expanded at the tumor si te. The corresponding clone was isolated in vitro and found to be a CD8(+) cytotoxic T lymphocyte with a strong and selective cytolytic activity again st the autologous tumor cell line. Here, we demonstrate that this predomina nt V beta 16(+) tumorinfiltrating lymphocyte recognizes a peptide encoded b y a novel unconventional myosin class I gene. This peptide includes a mutat ion due to a single nucleotide substitution. The resulting Glu-->Lys replac ement at position 911 of the coding sequence is critical to generate the re cognized T cell epitope. These experiments demonstrate the existence of a n atural tumor-specific cytolytic T cell response in a primary regressing hum an melanoma lesion.