The gp100
melanoma-associated
tumor Ag was selected as a model system to study the diversity of human antitumor cytotoxic T cell responses. First,
peptides corresponding to dominant gp100 HLA-A2.1-restricted CTL
epitopes were tested using lymphocytes from normal volunteers and an in vitro priming protocol that uses
peptide-pulsed dendritic cells as APCs and
IL-7 and
IL-10 as immune-enhancing
cytokines. High CTL activity toward both
peptide-pulsed target cells and gp100+
melanoma cells was obtained with four out of five
peptides tested. Second, HLA-A2.1-binding
peptides from gp100 that do not appear to represent CTL
epitopes in
melanoma patients were also tested for their capacity to induce CTL using the in vitro priming protocol. Three of six
peptides tested induced CTL in lymphocytes from normal volunteers. One of these
peptides was also immunogenic for lymphocytes derived from a
melanoma patient in remission. Because these three CTL
epitopes were not recognized in the natural immune response in
melanoma patients but do appear as immunogens when
peptides are used to induce the T cell response, they may be considered as typical "subdominant"
epitopes. The results are discussed in the context of the usefulness of this approach to detail the immunologic potential of a given
tumor-associated Ag and its relevance for the design of effective immune-based
therapies.