Melan-A/MART-1_(51-73) represents an immunogenic HLA-DR4-restricted epitope recognized by melanoma-reactive CD4~+ T cells

摘要

The human Melan-A/MART-1 gene encodes an HLA-A2-restricted peptide epitope recognized by melanoma-reactive CD8~+ cytotoxic T lymphocytes. Here we report that this gene also encodes at least one HLA-DR4-presented peptide recognized by CD4~+ T cells. The Melan-A/MART-151--73 peptide was able to induce the in vitro expansion of specific CD4~+ T cells derived from normal DR4~+ donors or from DR4~+ patients with melanoma when pulsed onto autologous dendritic cells. CD4~+ responder T cells specifically produced IFN-γ in response to, and also lysed, T2.DR4 cells pulsed with the Melan-A/MART-1_(51-73) peptide and DR4~+ melanoma tar- get cells naturally expressing the Melan-A/MART-1 gene product. Interestingly, CD4~+ T cell immunoreactivity against the Melan-A/ MART-1_(51-73) peptide typically coexisted with a high frequency of anti-Melan-A/MART-1_(27-35) reactive CD8~+ T cells in freshly isolated blood harvested from HLA-A2~+/DR4~+ patients with melanoma. Taken together, these data support the use of this Melan-A/ MART-1 DR4-restricted melanoma epitope in future immunother- apeutic trials designed to generate, augment, and quantitate specific CD4~+ T cell responses against melanoma in vivo.