title: Melan-A/MART-1(51-73) represents an immunogenic HLA-DR4-restricted epitope recognized by melanoma-reactive CD4(+) T cells.
abstract: 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-1(51-73) 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-gamma in response to, and also lysed, T2.DR4 cells pulsed with the Melan-A/MART-1(51-73) peptide and DR4(+) melanoma target 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 immunotherapeutic trials designed to generate, augment, and quantitate specific CD4(+) T cell responses against melanoma in vivo.
authors.affiliation: Department of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA. zarourhm@msx.upmc.edu
authors.forename: H M
authors.initials: HM
authors.lastname: Zarour
authors.forename: J M
authors.initials: JM
authors.lastname: Kirkwood
authors.forename: L S
authors.initials: LS
authors.lastname: Kierstead
authors.forename: W
authors.initials: W
authors.lastname: Herr
authors.forename: V
authors.initials: V
authors.lastname: Brusic
authors.forename: C L
authors.initials: CL
authors.lastname: Slingluff
authors.forename: J
authors.initials: J
authors.lastname: Sidney
authors.forename: A
authors.initials: A
authors.lastname: Sette
authors.forename: W J
authors.initials: WJ
authors.lastname: Storkus
mesh_terms: D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use; D000939:Epitopes; D015804:HLA-DR4 Antigen / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis; D058965:MART-1 Antigen; D008545:Melanoma / Q000276:immunology*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000276:immunology*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D000939:Epitopes; D015804:HLA-DR4 Antigen; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D007371:Interferon-gamma