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

The human Melan-A/MART-1 gene encodes an HLA-A2-restricted peptide epitope recognized by melanoma-reactive CD8(+) cytotoxic T lymphocytes. Here we rep ort that this gene also encodes at least one HLA-DR4-presented peptide reco gnized by CD4(+) T cells. The Melan-A/MART-1(51-73) peptide was able to ind uce the in vitro expansion of specific CD4(+) T cells derived from normal D R4(+) donors or from DR4(+) patients with melanoma when pulsed onto autolog ous dendritic cells. CD4(+) responder T cells specifically produced IFN-gam ma in response to, and also lysed, T2.DR4 cells pulsed with the Melan-A/MAR T-1(51-73) peptide and DR4(+) melanoma target cells naturally expressing th e Melan-A/MART-1 gene product. Interestingly, CD4(+) T cell immunoreactivit y 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. Tak en together, these data support the use of this Melan-A/MART-1 DR4-restrict ed melanoma epitope in future immunotherapeutic trials designed to generate , augment, and quantitate specific CD4(+) T cell responses against melanoma in vivo.